USP26 affects AR

3 1 | 1 16 7 1

USP26 binds AR.

3 | 9 7 1

USP26 binds AR. 10 / 17

3 | 9 4

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"Our study also provides the evidence on the interactions between USP26 and AR in mouse testis, whereby pointing to a potential mechanism."

30561524

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➶

reach

"As an example, USP26 physically interacts with AR and influences AR ubiquitination and transcriptional activation [XREF_BIBR]."

29353883

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➶

sparser

"Usp26 can directly bind and deubiquitinate AR, acting as a co-regulator of the AR by reversing AR activation and degradation by MDM2 ubiquitination depending on cellular context highlighting the complexity of post-translational regulation [ xref ]."

25962961

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➶

sparser

"For example, USP26 physically interacts with AR and influences AR ubiquitination and transcriptional activation; xref USP12 stabilizes AR, enhances its cellular function, and thereby triggers the gene expression of PSA. xref In addition, USP10 also has been reported to bind AR, resulting in increased transcriptional activity."

28151478

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➶

reach

"Usp26 binds to AR via nuclear receptor boxes, a hydrophobic motif (LXXLL) found in p160 coactivators."

21820033

---

➶

reach

"For example, USP26 physically interacts with AR and influences AR ubiquitination and transcriptional activation; 17 USP12 stabilizes AR, enhances its cellular function, and thereby triggers the gene expression of PSA."

28151478

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➶

biogrid

No evidence text available

27089915

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➶

sparser

"Our study also provides the evidence on the interactions between USP26 and AR in mouse testis, whereby pointing to a potential mechanism."

30561524

---

➶

reach

"Given USP26 interaction with the androgen receptor, we conducted this study to characterize USP26 as a potential target affecting human testicular function and fertility and androgen dependent cancers."

24922532

---

➶

sparser

"As an example, USP26 physically interacts with AR and influences AR ubiquitination and transcriptional activation [ xref ]."

29353883

USP26 binds AR and nuclear receptor. 2 / 2

| 2

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➶

sparser

"USP26 binds to androgen receptor through three nuclear receptor interaction motifs, and knockdown of USP26 leads to decreased receptor activity in LnCaP and HEK293 cells (Dirac and Bernards, xref )."

28381987

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sparser

"Usp26 binds to AR via nuclear receptor boxes, a hydrophobic motif (LXXLL) found in p160 coactivators."

21820033

AR binds USP26. 1 / 1

| 1

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➶

isi

"Moreover, the results from co-immunoprecipitation (CO-IP), immunofluorescence and western blot assays showed that the physiological process due to USP26 interacted with AR and influenced AR deubiquitination, thus upregulating the proteins CCND1 and SPATA46 - which are associated with cell cycle progression and spermatogenesis - as well as decreasing the expression of TP73."

33064378

USP26 binds TBCB and AR. 1 / 1

| 1

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➶

sparser

"Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity."

20501646

USP26 deubiquitinates AR.

1 | 1 4

USP26 deubiquitinates AR. 6 / 6

1 | 1 4

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reach

"Taken together, the effects of AR deubiquitinated by USP26 could modulate sperm maturation and spermatogenesis through the androgen receptor signaling pathway."

33064378

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➶

reach

"USP26 can deubiquitylate AR in the presence of androgen, while USP10 and 2A-DUB both regulate AR transcriptional activity but do not alter protein stability."

24197134

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➶

reach

"USP26 deubiquitinates androgen receptor (AR) in the maintenance of sperm maturation and spermatogenesis through the androgen receptor signaling pathway."

33064378

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reach

"Elevated cellular ROS levels might then inhibit USP26 activity to increase the ubiquitination of androgen receptor (AR) and AR splice variant 7 (ARv7) and their ubiquitin and proteasome dependent degradation, which contributed to the increase of Enz sensitivity."

32235588

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➶

trips

"USP26 deubiquitinates androgen receptor (AR) in the maintenance of sperm maturation and spermatogenesis through the androgen receptor signaling pathway."

33064378

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➶

ubibrowser

"Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity."

20501646

USP26 ubiquitinates AR.

| 1

USP26 ubiquitinates AR. 1 / 1

| 1

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➶

reach

"Elevated cellular ROS levels might then inhibit USP26 activity to increase the ubiquitination of androgen receptor (AR) and AR splice variant 7 (ARv7) and their ubiquitin and proteasome dependent degradation, which contributed to the increase of Enz sensitivity."

32235588

USP26 decreases the amount of AR.

| 1

USP26 decreases the amount of AR. 1 / 1

| 1

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➶

reach

"To further dissect the molecular mechanism (s) how miR-367-3p increases AR expression, according to the screening strategy and bioinformatics analysis, we focused on the 2 miR-367-3p predicted targets, MDM2 and USP26, that were reported to modulate AR protein expression."

27688096

USP26 activates AR.

| 1

USP26 activates AR. 1 / 1

| 1

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➶

reach

"In LNCaP cells, Usp26 depletion by siRNA enhances AR dependent transcription, suggesting it acts on a factor that is negatively regulated by ubiquitination (Dirac and Bernards, 2010)."

21820033

USP26 affects RLIM

| 28

RLIM binds USP26. 10 / 28

| 28

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sparser

"Our results thus far indicated that the RNF12-USP26 axis specifically operates in the testes and promotes the expression of genes associated with gametogenesis."

35857630

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sparser

"Finally, we investigated whether the RNF12-USP26 axis is dysregulated in human disease."

35857630

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sparser

"Furthermore, this RNF12-USP26 axis was disrupted by RLIM and USP26 variants found in TOKAS and infertility patients, respectively."

35857630

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sparser

"Finally, we showed that the RNF12-USP26 axis operated specifically in the testes and was disrupted in human genetic disorders associated with genital abnormalities and/or infertility."

35857630

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"These data suggest that the RNF12-USP26 axis may function to promote the expression of genes that are required for gametogenesis and germ cell development, consistent with a functional role for the RNF12-USP26 axis in the testes."

35857630

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"Notably, Usp26 expression was largely dependent on RNF12 in these experiments ( xref ), confirming that the RNF12-USP26 axis is operational in the context of PGCLC differentiation."

35857630

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sparser

"This RNF12-USP26 amplification loop specifically operated in testes and promoted efficient expression of genes that were associated with gametogenesis and germ cell differentiation in vitro, including Dazl ( xref ), Usp9y ( xref ), and Dppa3 ( xref )."

35857630

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sparser

"We therefore hypothesized that USP26 variants identified from azoospermia patients may also lead to deregulation of the RNF12-USP26 axis and gametogenesis gene expression."

35857630

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"To determine the impact of a TOKAS-associated RNF12 variant on the regulation and function of the RNF12-USP26 axis, we took advantage of knock-in mESCs harboring the mouse equivalent of the human RNF12 R599C variant identified from a TOKAS patient kindred (RNF12 R575C-KI) ( xref )."

35857630

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"Our data therefore demonstrate that a RNF12 TOKAS variant disrupts expression of Usp26 and other gametogenesis genes, suggesting that the RNF12-USP26 axis is likely impaired in patients harboring a disease-causing variant of RNF12."

35857630

USP26 affects CBX4

1 | 8 9

USP26 binds CBX4.

1 | 6 9

USP26 binds CBX4. 7 / 8

1 | 6

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reach

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR and Cas9 technology."

28839133

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reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

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reach

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog, and Cbx7 were observed, suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

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➶

reach

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells, suggesting that USP26 and CBX4 or CBX6 interactions are RING1A independent."

28839133

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➶

reach

"USP26 binds to CBX4 and CBX6 in RING1A independent manner."

28839133

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biogrid

No evidence text available

28839133

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➶

reach

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs."

28839133

USP26 binds CBX4 and CBX6. 5 / 5

| 5

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sparser

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs (Fig.  xref )."

28839133

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sparser

"Taken together, these results suggest that USP26 physically binds to components of the PRC1 complex, including RING1A, CBX4, and CBX6, and the interaction between USP26 and CBX4 or CBX6 is independent of the presence of RING1A."

28839133

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sparser

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells (Fig.  xref ), suggesting that USP26 and CBX4 or CBX6 interactions are RING1A-independent."

28839133

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sparser

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog , and Cbx7 were observed (Supplementary Fig.  xref ), suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

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sparser

"However, the interaction of USP26 with CBX4 and CBX6 was independent of RING1A. In differentiated cells, USP26 removed K48-linked Ub chains from CBX4 and CBX6, thus stabilizing the proteins and preventing their degradation."

28839133

RING1 binds USP26, CBX4, and CBX6. 2 / 2

| 2

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sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

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sparser

"USP26 binds to CBX4 and CBX6 in RING1A-independent manner."

28839133

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

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➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

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➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

USP26 activates CBX4.

| 2

USP26 activates CBX4. 2 / 4

| 2

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➶

reach

"This result suggests that the increased Usp26 expression during ESC differentiation may lead to increased CBX4 and CBX6 protein expression not only by CBX4 and CBX6 protein stabilization but also indirectly by reversing the repression of their gene expression."

28839133

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➶

reach

"Taken together, these results provide molecular mechanisms of Usp26 mediated increased CBX4 and CBX6 protein stability for suppressing pluripotent gene expression."

28839133

AR affects USP26

3 | 9 7 1

USP26 binds AR. 10 / 17

3 | 9 4

---

➶

reach

"Our study also provides the evidence on the interactions between USP26 and AR in mouse testis, whereby pointing to a potential mechanism."

30561524

---

➶

reach

"As an example, USP26 physically interacts with AR and influences AR ubiquitination and transcriptional activation [XREF_BIBR]."

29353883

---

➶

sparser

"Usp26 can directly bind and deubiquitinate AR, acting as a co-regulator of the AR by reversing AR activation and degradation by MDM2 ubiquitination depending on cellular context highlighting the complexity of post-translational regulation [ xref ]."

25962961

---

➶

sparser

"For example, USP26 physically interacts with AR and influences AR ubiquitination and transcriptional activation; xref USP12 stabilizes AR, enhances its cellular function, and thereby triggers the gene expression of PSA. xref In addition, USP10 also has been reported to bind AR, resulting in increased transcriptional activity."

28151478

---

➶

reach

"Usp26 binds to AR via nuclear receptor boxes, a hydrophobic motif (LXXLL) found in p160 coactivators."

21820033

---

➶

reach

"For example, USP26 physically interacts with AR and influences AR ubiquitination and transcriptional activation; 17 USP12 stabilizes AR, enhances its cellular function, and thereby triggers the gene expression of PSA."

28151478

---

➶

biogrid

No evidence text available

27089915

---

➶

sparser

"Our study also provides the evidence on the interactions between USP26 and AR in mouse testis, whereby pointing to a potential mechanism."

30561524

---

➶

reach

"Given USP26 interaction with the androgen receptor, we conducted this study to characterize USP26 as a potential target affecting human testicular function and fertility and androgen dependent cancers."

24922532

---

➶

sparser

"As an example, USP26 physically interacts with AR and influences AR ubiquitination and transcriptional activation [ xref ]."

29353883

USP26 binds AR and nuclear receptor. 2 / 2

| 2

---

➶

sparser

"USP26 binds to androgen receptor through three nuclear receptor interaction motifs, and knockdown of USP26 leads to decreased receptor activity in LnCaP and HEK293 cells (Dirac and Bernards, xref )."

28381987

---

➶

sparser

"Usp26 binds to AR via nuclear receptor boxes, a hydrophobic motif (LXXLL) found in p160 coactivators."

21820033

AR binds USP26. 1 / 1

| 1

---

➶

isi

"Moreover, the results from co-immunoprecipitation (CO-IP), immunofluorescence and western blot assays showed that the physiological process due to USP26 interacted with AR and influenced AR deubiquitination, thus upregulating the proteins CCND1 and SPATA46 - which are associated with cell cycle progression and spermatogenesis - as well as decreasing the expression of TP73."

33064378

USP26 binds TBCB and AR. 1 / 1

| 1

---

➶

sparser

"Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity."

20501646

USP26 affects CBX6

1 | 6 9

USP26 binds CBX6.

1 | 5 9

USP26 binds CBX6. 6 / 7

1 | 5

---

➶

reach

"USP26 binds to CBX4 and CBX6 in RING1A independent manner."

28839133

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

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➶

biogrid

No evidence text available

28839133

---

➶

reach

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR and Cas9 technology."

28839133

---

➶

reach

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs."

28839133

---

➶

reach

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog, and Cbx7 were observed, suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

USP26 binds CBX4 and CBX6. 5 / 5

| 5

---

➶

sparser

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs (Fig.  xref )."

28839133

---

➶

sparser

"Taken together, these results suggest that USP26 physically binds to components of the PRC1 complex, including RING1A, CBX4, and CBX6, and the interaction between USP26 and CBX4 or CBX6 is independent of the presence of RING1A."

28839133

---

➶

sparser

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells (Fig.  xref ), suggesting that USP26 and CBX4 or CBX6 interactions are RING1A-independent."

28839133

---

➶

sparser

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog , and Cbx7 were observed (Supplementary Fig.  xref ), suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

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➶

sparser

"However, the interaction of USP26 with CBX4 and CBX6 was independent of RING1A. In differentiated cells, USP26 removed K48-linked Ub chains from CBX4 and CBX6, thus stabilizing the proteins and preventing their degradation."

28839133

RING1 binds USP26, CBX4, and CBX6. 2 / 2

| 2

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➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

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➶

sparser

"USP26 binds to CBX4 and CBX6 in RING1A-independent manner."

28839133

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

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➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

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➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

USP26 activates CBX6.

| 1

USP26 activates CBX6. 1 / 3

| 1

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➶

reach

"Taken together, these results provide molecular mechanisms of Usp26 mediated increased CBX4 and CBX6 protein stability for suppressing pluripotent gene expression."

28839133

USP26 affects SMAD7

1 | 12 4

USP26 binds SMAD7.

| 2 4

USP26 binds SMAD7. 5 / 5

| 2 3

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reach

"TGF-beta treatment enhanced the binding of USP26 to SMAD7 but not SMAD6 (Fig XREF_FIG C and D)."

28381482

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➶

sparser

"TGF‐β treatment enhanced the binding of USP26 to SMAD7 but not SMAD6 (Fig  xref C and D)."

28381482

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reach

"Therefore, in light of our findings that both USP26 and SMAD7 are upregulated following stimulation with TGF-beta, we speculated that USP26 might form a complex with SMAD7 following TGF-beta exposure leading to USP26 mediated deubiquitination."

28381482

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➶

sparser

"Having shown that USP26 is induced by RAC1B and that its knockdown decreased SMAD7 protein abundance, it remains to be determined whether in pancreatic carcinoma cells USP26 indeed binds to and deubiquitinates SMAD7, as shown previously in breast cancer and glioma cells [ xref ]."

32545415

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➶

sparser

"Therefore, in light of our findings that both USP26 and SMAD7 are upregulated following stimulation with TGF‐β, we speculated that USP26 might form a complex with SMAD7 following TGF‐β exposure leading to USP26‐mediated deubiquitination."

28381482

USP26 binds SMAD3, SMAD6, and SMAD7. 1 / 1

| 1

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➶

sparser

"These data suggest that USP26 can form a stable complex in vivo with SMAD3, SMAD6, and SMAD7."

28381482

USP26 deubiquitinates SMAD7.

1 | 2

USP26 deubiquitinates SMAD7. 3 / 3

1 | 2

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➶

reach

"Examples include ubiquitin specific protease 10 (USP10), which can act on SMAD4 to make it deubiquitinated and stable, further promoting TGF-beta signaling [XREF_BIBR], and USP26, which promotes SMAD7 deubiquitination, thereby amplifying the inhibitory effect of SMAD7 and strengthening the inhibition of the TGF-beta signaling pathway [XREF_BIBR]."

34335834

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➶

ubibrowser

"USP26 regulates TGF-b signaling by deubiquitinating and stabilizing SMAD7."

28381482

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➶

reach

"USP26 deubiquitinates SMAD7."

28381482

USP26 activates SMAD7.

| 3

USP26 activates SMAD7. 3 / 3

| 3

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➶

reach

"Conversely, knockdown of USP26 rapidly degrades SMAD7 resulting in TGF-beta receptor stabilization and enhanced levels of p-SMAD2."

28381482

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➶

reach

"In contrast, loss of USP26 rapidly degrades SMAD7 stabilizing the TGF-beta receptors leading to enhanced TGF-beta activity as observed by increased levels of phosphorylated SMAD2."

28381482

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➶

reach

"As loss of USP26 degrades SMAD7 leading to the stabilization of TbetaR, we evaluated the role of TbetaR and SMAD7 on clinical outcome."

28381482

USP26 inhibits SMAD7.

| 2

USP26 inhibits SMAD7. 2 / 2

| 2

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➶

reach

"As observed with USP26 knockdown, ectopic expression of the DUB dead mutant recapitulated the augmentation of SMAD7 induction by TGF-beta whereas wild-type USP26 significantly diminished the induction of SMAD7 in the presence of TGF-beta (Fig XREF_FIG F)."

28381482

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➶

reach

"Therefore, we analyzed whether loss of USP26 increases the levels of SMAD7 Lys48 or Lys63 incorporated ubiquitin chains."

28381482

USP26 increases the amount of SMAD7.

| 2

Modified mutated USP26 increases the amount of SMAD7. 1 / 1

| 1

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➶

reach

"Overexpression of USP26, but not the catalytically inactive mutant USP26 C/S, markedly increased the expression of SMAD7 (Fig XREF_FIG A)."

28381482

Modified USP26 increases the amount of SMAD7. 1 / 1

| 1

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➶

reach

"Overexpression of USP26, but not the catalytically inactive mutant USP26 C/S, markedly increased the expression of SMAD7 (Fig XREF_FIG A)."

28381482

USP26 decreases the amount of SMAD7.

| 1

USP26 decreases the amount of SMAD7. 1 / 1

| 1

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➶

reach

"In addition, depletion of USP26 significantly reduced the expression of SMAD7 in both the MDA-MB-231 and U373 cell lines (Fig XREF_FIG F and G)."

28381482

CBX4 affects USP26

1 | 6 9

USP26 binds CBX4. 7 / 8

1 | 6

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➶

reach

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR and Cas9 technology."

28839133

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

---

➶

reach

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog, and Cbx7 were observed, suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

---

➶

reach

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells, suggesting that USP26 and CBX4 or CBX6 interactions are RING1A independent."

28839133

---

➶

reach

"USP26 binds to CBX4 and CBX6 in RING1A independent manner."

28839133

---

➶

biogrid

No evidence text available

28839133

---

➶

reach

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs."

28839133

USP26 binds CBX4 and CBX6. 5 / 5

| 5

---

➶

sparser

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs (Fig.  xref )."

28839133

---

➶

sparser

"Taken together, these results suggest that USP26 physically binds to components of the PRC1 complex, including RING1A, CBX4, and CBX6, and the interaction between USP26 and CBX4 or CBX6 is independent of the presence of RING1A."

28839133

---

➶

sparser

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells (Fig.  xref ), suggesting that USP26 and CBX4 or CBX6 interactions are RING1A-independent."

28839133

---

➶

sparser

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog , and Cbx7 were observed (Supplementary Fig.  xref ), suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

---

➶

sparser

"However, the interaction of USP26 with CBX4 and CBX6 was independent of RING1A. In differentiated cells, USP26 removed K48-linked Ub chains from CBX4 and CBX6, thus stabilizing the proteins and preventing their degradation."

28839133

RING1 binds USP26, CBX4, and CBX6. 2 / 2

| 2

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➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

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➶

sparser

"USP26 binds to CBX4 and CBX6 in RING1A-independent manner."

28839133

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

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➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

CBX6 affects USP26

1 | 5 9

USP26 binds CBX6. 6 / 7

1 | 5

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➶

reach

"USP26 binds to CBX4 and CBX6 in RING1A independent manner."

28839133

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reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

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➶

biogrid

No evidence text available

28839133

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➶

reach

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR and Cas9 technology."

28839133

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➶

reach

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs."

28839133

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➶

reach

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog, and Cbx7 were observed, suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

USP26 binds CBX4 and CBX6. 5 / 5

| 5

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➶

sparser

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs (Fig.  xref )."

28839133

---

➶

sparser

"Taken together, these results suggest that USP26 physically binds to components of the PRC1 complex, including RING1A, CBX4, and CBX6, and the interaction between USP26 and CBX4 or CBX6 is independent of the presence of RING1A."

28839133

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➶

sparser

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells (Fig.  xref ), suggesting that USP26 and CBX4 or CBX6 interactions are RING1A-independent."

28839133

---

➶

sparser

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog , and Cbx7 were observed (Supplementary Fig.  xref ), suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

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➶

sparser

"However, the interaction of USP26 with CBX4 and CBX6 was independent of RING1A. In differentiated cells, USP26 removed K48-linked Ub chains from CBX4 and CBX6, thus stabilizing the proteins and preventing their degradation."

28839133

RING1 binds USP26, CBX4, and CBX6. 2 / 2

| 2

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➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

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➶

sparser

"USP26 binds to CBX4 and CBX6 in RING1A-independent manner."

28839133

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

USP26 affects MDM2

1 1 | 2 5 2

USP26 binds MDM2.

1 | 1 3 2

USP26 binds MDM2. 7 / 8

1 | 1 3 2

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➶

sparser

"The interaction between USP26 and Mdm2, and the subsequent deubiquitination of Mdm2, serves, most probably to regulate Mdm2."

27810359

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➶

reach

"Future therapeutic modalities that interfere with the association between USP26 and Mdm2 will be used to destabilize the ligase in malignancies where it is upregulated."

27810359

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➶

reach

"We found that USP26 binds to Mdm2 through its coiled coiled C-terminal domain."

27810359

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➶

sparser

"We found that USP26 binds to Mdm2 through its coiled-coiled C-terminal domain."

27810359

---

➶

biogrid

No evidence text available

27810359

---

➶

trips

"We found that USP26 binds to Mdm2 through its coiled-coiled C-terminal domain."

27810359

---

➶

reach

"The interaction between USP26 and Mdm2, and the subsequent deubiquitination of Mdm2, serves, most probably to regulate Mdm2."

27810359

USP26 deubiquitinates MDM2.

1 | 1 2

USP26 deubiquitinates MDM2. 4 / 4

1 | 1 2

---

➶

trips

"USP26 deubiquitinates Mdm2 and stabilizes it."

27810359

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➶

reach

"USP26 also deubiquitinates and stabilizes Mdm2 [70] thus underlining the complex regulation of AR transcriptional activity."

30217566

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➶

ubibrowser

"Review"

28801249

---

➶

reach

"USP26 deubiquitinates Mdm2 and stabilizes it."

27810359

USP26 affects PRC1

1 | 1 4

USP26 binds PRC1.

| 4

USP26 binds PRC1. 2 / 6

| 2

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➶

sparser

"Taken together, these results suggest that USP26 physically binds to components of the PRC1 complex, including RING1A, CBX4, and CBX6, and the interaction between USP26 and CBX4 or CBX6 is independent of the presence of RING1A."

28839133

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➶

sparser

"To understand how Usp26 expression is regulated, we assessed the promoter-binding activity of Usp26 by PRC1 subunits using the ChIP–qPCR assay during RA-induced ESC differentiation, and observed that PRC1 components PCGF2 and Cbx7 occupation as well as H2A-ubi1 modifications decreased significantly in Usp26 promoter (Supplementary Fig. xref d), thus indicating that CBX7 containing PRC1 complex is a potential repressor of Usp26 ."

28839133

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

USP26 deubiquitinates PRC1.

1 | 1

USP26 deubiquitinates PRC1. 2 / 2

1 | 1

---

➶

ubibrowser

"Review"

29142505

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reach

"In some cancer types, PRC1 can be deubiquitinated by USP7, USP11 and USP26 [XREF_BIBR, XREF_BIBR]."

29142505

CBX6 affects CBX4

| 9

USP26 binds CBX4 and CBX6. 5 / 5

| 5

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➶

sparser

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs (Fig.  xref )."

28839133

---

➶

sparser

"Taken together, these results suggest that USP26 physically binds to components of the PRC1 complex, including RING1A, CBX4, and CBX6, and the interaction between USP26 and CBX4 or CBX6 is independent of the presence of RING1A."

28839133

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➶

sparser

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells (Fig.  xref ), suggesting that USP26 and CBX4 or CBX6 interactions are RING1A-independent."

28839133

---

➶

sparser

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog , and Cbx7 were observed (Supplementary Fig.  xref ), suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

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➶

sparser

"However, the interaction of USP26 with CBX4 and CBX6 was independent of RING1A. In differentiated cells, USP26 removed K48-linked Ub chains from CBX4 and CBX6, thus stabilizing the proteins and preventing their degradation."

28839133

RING1 binds USP26, CBX4, and CBX6. 2 / 2

| 2

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➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

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sparser

"USP26 binds to CBX4 and CBX6 in RING1A-independent manner."

28839133

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

USP26 affects homologous recombination

| 8

USP26 activates homologous recombination.

| 5

USP26 activates homologous recombination. 5 / 5

| 5

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reach

"Given that USP26 and USP37 are able to reverse RNF8/168 mediated ubiquitylation and promote HR, these enzymes would be ideal candidates to facilitate the repositioning of ubiquitylated substrates away from the DSB."

26101254

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reach

"A striking conclusion from our study is that both over-expression as well as knockdown of USP26 or USP37 impairs HR."

26101254

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➶

reach

"Loss of USP26 and USP37 function markedly impairs the assembly of PALB2, RAD51 and efficient HR."

26101254

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➶

reach

"Interestingly, in contrast with initial findings assessing overexpression of these DUBs, knockdown of either USP26 or USP37 impairs accumulation of key HR factors including RAD51 as well as PALB2, CtIP, and RPA [154]."

32708614

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➶

reach

"Loss of USP26 or USP37 impairs HR by counteracting RAP80 dependent sequestration of BRCA1."

26101254

USP26 inhibits homologous recombination.

| 2

USP26 inhibits homologous recombination. 2 / 2

| 2

---

➶

reach

"Depletion of USP26 or USP37 disrupts the execution of HR and this effect is alleviated by the simultaneous depletion of RAP80."

26101254

---

➶

reach

"We reasoned that USP26 and USP37 may antagonize the RAP80 dependent sequestration of BRCA1 by removing RNF8 and RNF168 mediated ubiquitylation and thereby promote HR."

26101254

USP26 increases the amount of homologous recombination.

| 1

USP26 increases the amount of homologous recombination. 1 / 1

| 1

---

➶

reach

"Moreover, co-depletion of either USP26 or USP37 and RAP80 was able to restore levels of HR."

32708614

USP26 affects cell differentiation

| 8

USP26 activates cell differentiation.

| 7

USP26 activates cell differentiation. 7 / 7

| 7

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➶

reach

"Conversely, lesser extent of CBX7 protein binding to the promoters of Cbx4 and Cbx6 is observed during Usp26 mediated ESC differentiation and RA induced ESC differentiation."

28839133

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➶

reach

"Correlative with the Oct4 gene expression data, occupancy at the Oct4 promoter by USP26, CBX4, CBX6, and H2A-ubi1 was low even during USP26 mediated ESC differentiation."

28839133

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reach

"These results suggest that USP26 expression promotes ESC differentiation."

28839133

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➶

reach

"USP26 expression promotes ESC differentiation."

28839133

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➶

reach

"Furthermore, infection of ESCs with GFP tagged mouse (m) USP26 led to ESC differentiation in an RA independent manner."

28839133

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reach

"Using screening of shRNA specific for the DUB subfamily USPs, we identified a novel cellular reprogramming repressor gene Usp26, which blocked somatic cell reprogramming into iPSCs and promoted differentiation by stabilizing PRC1 complexes."

28839133

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➶

reach

"We also found significant decrease in the gene expression of Cbx7, a Polycomb protein, upon Usp26 induced ESC differentiation."

28839133

USP26 inhibits cell differentiation.

| 1

USP26 inhibits cell differentiation. 1 / 1

| 1

---

➶

reach

"Mechanistically, USP26 stabilizes β-catenin to promote the osteogenic activity of mesenchymal cells (MSCs) and impairs the osteoclastic differentiation of bone myelomonocytes (BMMs) by stabilizing inhibitors of NF-κBα (IκBα)."

35091692

USP26 affects BRCA1

| 8

USP26 inhibits BRCA1.

| 5

USP26 inhibits BRCA1. 5 / 5

| 5

---

➶

reach

"We reasoned that USP26 and USP37 may antagonize the RAP80 dependent sequestration of BRCA1 by removing RNF8 and RNF168 mediated ubiquitylation and thereby promote HR."

26101254

---

➶

reach

"USP26 and USP37 limit the ubiquitin-dependent sequestration of BRCA1 and facilitate BRCA1-PALB2-BRCA2-RAD51 association at damaged chromatin to promote HR repair [77]."

33797206

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➶

reach

"USP26 and USP37 have additionally been shown to impair accumulation of RAP80 and BRCA1 [154]."

32708614

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➶

reach

"Together, these results suggest that USP26 and USP37 promote the BRCA1 dependent loading of PALB2 and RAD51 by counteracting the repressive impact of RAP80 dependent BRCA1 sequestration and RAP80 dependent inhibition of end-resection during HR."

26101254

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➶

reach

"In agreement with this hypothesis, we found that USP26 or USP37 depletion inhibits the efficient association of BRCA1 with PALB2, a unique subunit of the BRCC complex."

26101254

USP26 activates BRCA1.

| 3

USP26 activates BRCA1. 3 / 3

| 3

---

➶

reach

"On the other hand, we also found that USP26 and USP37 promote the efficient association of BRCA1 with PALB2."

26101254

---

➶

reach

"Together, these results suggest that USP26 and USP37 promote the BRCA1 dependent loading of PALB2 and RAD51 by counteracting the repressive impact of RAP80 dependent BRCA1 sequestration and RAP80 dependent inhibition of end-resection during HR."

26101254

---

➶

reach

"Loss of USP26 or USP37 impairs HR by counteracting RAP80 dependent sequestration of BRCA1."

26101254

PRC1 affects USP26

| 4

USP26 binds PRC1. 2 / 6

| 2

---

➶

sparser

"Taken together, these results suggest that USP26 physically binds to components of the PRC1 complex, including RING1A, CBX4, and CBX6, and the interaction between USP26 and CBX4 or CBX6 is independent of the presence of RING1A."

28839133

---

➶

sparser

"To understand how Usp26 expression is regulated, we assessed the promoter-binding activity of Usp26 by PRC1 subunits using the ChIP–qPCR assay during RA-induced ESC differentiation, and observed that PRC1 components PCGF2 and Cbx7 occupation as well as H2A-ubi1 modifications decreased significantly in Usp26 promoter (Supplementary Fig. xref d), thus indicating that CBX7 containing PRC1 complex is a potential repressor of Usp26 ."

28839133

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

MDM2 affects USP26

1 | 1 3 2

USP26 binds MDM2. 7 / 8

1 | 1 3 2

---

➶

sparser

"The interaction between USP26 and Mdm2, and the subsequent deubiquitination of Mdm2, serves, most probably to regulate Mdm2."

27810359

---

➶

reach

"Future therapeutic modalities that interfere with the association between USP26 and Mdm2 will be used to destabilize the ligase in malignancies where it is upregulated."

27810359

---

➶

reach

"We found that USP26 binds to Mdm2 through its coiled coiled C-terminal domain."

27810359

---

➶

sparser

"We found that USP26 binds to Mdm2 through its coiled-coiled C-terminal domain."

27810359

---

➶

biogrid

No evidence text available

27810359

---

➶

trips

"We found that USP26 binds to Mdm2 through its coiled-coiled C-terminal domain."

27810359

---

➶

reach

"The interaction between USP26 and Mdm2, and the subsequent deubiquitination of Mdm2, serves, most probably to regulate Mdm2."

27810359

USP26 affects TGFB

| 7

USP26 inhibits TGFB.

| 5

USP26 inhibits TGFB. 5 / 5

| 5

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➶

reach

"Taken together, these data indicate that USP26 inhibits TGF-beta pathway activity by limiting Lys48 ubiquitin mediated degradation of SMAD7 consequently resulting in enhanced ubiquitylation and degradation of the TbetaR complex."

28381482

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➶

reach

"As knockdown of USP26 potently activated the TGF-beta pathway in breast cancer, we investigated whether depletion of USP26 in the TGF-beta-responsive metastatic cell line MDA-MB-231 enhanced cellular motility and invasion."

28381482

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➶

reach

"In line with our other models, knockdown of USP26 in this patient derived cell line enhanced TGF-beta activity as evidenced by increased levels of phospho-SMAD2 and increased expression of TGF-beta target genes CTGF, LIF, and SMAD7 (Fig XREF_FIG D and E)."

28381482

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➶

reach

"These results suggest that USP26 may potentially act in conjunction with SMAD7 and SMURF2 to downregulate canonical TGF-beta signaling."

28381482

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➶

reach

"Taken together, these findings confirmed our hypothesis that loss of USP26 enhances TGF-beta signaling and confers poor prognosis in glioblastoma patients."

28381482

USP26 phosphorylates TGFB.

| 1

USP26 leads to the phosphorylation of TGFB. 1 / 1

| 1

---

➶

reach

"As USP26 appears to mediate SMAD2/3 phosphorylation and downstream TGF-beta activity, we reasoned that USP26 may function through the canonical TGF-beta pathway."

28381482

USP26 activates TGFB.

| 1

USP26 activates TGFB. 1 / 1

| 1

---

➶

reach

"USP26 depletion enhances TGF-beta activity and TGF-beta biological responses in breast cancer and glioma."

28381482

USP26 affects SOX2

| 5

USP26 binds SOX2.

| 2

SOX2 binds USP26. 2 / 3

| 2

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

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➶

reach

"Similarly, during RA induced ESC differentiation, USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 also bound to the Sox2, Nanog, and Cbx7 promoters."

28839133

USP26 inhibits SOX2.

| 1

USP26 inhibits SOX2. 1 / 2

| 1

---

➶

reach

"By contrast, knockdown of Usp26 enhances the efficiency of reprogramming by reactivating Sox2 and Nanog through degradation of CBX4 and CBX6."

28839133

USP26 decreases the amount of SOX2.

| 2

Modified USP26 decreases the amount of SOX2. 1 / 1

| 1

---

➶

reach

"Overexpression of Usp26 in ESCs led to decreased mRNA levels of Sox2, Nanog, and Oct4 compared with control cells."

28839133

USP26 decreases the amount of SOX2. 1 / 1

| 1

---

➶

reach

"Our results showed that after Usp26 knockdown during Dox induced OSKM mediated MEF reprogramming led to increased mRNA levels of Sox2 and Nanog, but not Oct4, compared with control."

28839133

USP26 affects NANOG

| 5

USP26 binds NANOG.

| 2

USP26 binds NANOG. 2 / 3

| 2

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

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➶

reach

"Similarly, during RA induced ESC differentiation, USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 also bound to the Sox2, Nanog, and Cbx7 promoters."

28839133

USP26 inhibits NANOG.

| 1

USP26 inhibits NANOG. 1 / 2

| 1

---

➶

reach

"By contrast, knockdown of Usp26 enhances the efficiency of reprogramming by reactivating Sox2 and Nanog through degradation of CBX4 and CBX6."

28839133

USP26 decreases the amount of NANOG.

| 1

USP26 decreases the amount of NANOG. 1 / 1

| 1

---

➶

reach

"Our results showed that after Usp26 knockdown during Dox induced OSKM mediated MEF reprogramming led to increased mRNA levels of Sox2 and Nanog, but not Oct4, compared with control."

28839133

USP26 activates NANOG.

| 1

Modified USP26 activates NANOG. 1 / 1

| 1

---

➶

reach

"Overexpression of Usp26 in ESCs led to decreased mRNA levels of Sox2, Nanog, and Oct4 compared with control cells."

28839133

TGFB affects USP26

| 7

TGFB increases the amount of USP26.

| 6

TGFB increases the amount of USP26. 6 / 6

| 6

---

➶

reach

"We demonstrate that TGF-beta rapidly enhances the expression of USP26 and reinforces SMAD7 stability by limiting the ubiquitin mediated turnover of SMAD7."

28381482

---

➶

reach

"TGF-β rapidly increases the expression of USP26 and stabilizes Smad7 by mediating its deubiquitination."

34059951

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➶

reach

"Our data suggest that as part of a negative feedback loop, TGF-beta enhances the expression of not only SMAD7 but also USP26, which acts to deubiquitinate and stabilize SMAD7."

28381482

---

➶

reach

"Further experimentation will be required to elucidate the precise mechanism of how TGF-beta enhances USP26 expression."

28381482

---

➶

reach

"In all cell lines tested, TGF-beta enhanced the mRNA expression levels of both USP26 and SMAD7."

28381482

---

➶

reach

"TGFbeta enhances the expression of USP26 and reinforces SMAD7 stability by limiting the ubiquitin mediated turnover of SMAD7."

33085646

TGFB activates USP26.

| 1

TGFB activates USP26. 1 / 1

| 1

---

➶

reach

"To verify whether USP26 induction by TGF-beta is prevalent in other cell types, we analyzed the induction of USP26 and SMAD7 at early time points in the TGF-beta-responsive breast cancer cell lines MCF7, MDA-MB-231, T47D, and CAL51 and glioma cell lines U373, PCTC, and A172 (Fig XREF_FIG A-G)."

28381482

USP26 affects RING1

| 4

RING1 binds USP26. 1 / 3

| 1

---

➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

RING1 binds USP26, CBX4, and CBX6. 2 / 2

| 2

---

➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

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➶

sparser

"USP26 binds to CBX4 and CBX6 in RING1A-independent manner."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

SMAD7 affects USP26

| 2 4

USP26 binds SMAD7. 5 / 5

| 2 3

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➶

reach

"TGF-beta treatment enhanced the binding of USP26 to SMAD7 but not SMAD6 (Fig XREF_FIG C and D)."

28381482

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➶

sparser

"TGF‐β treatment enhanced the binding of USP26 to SMAD7 but not SMAD6 (Fig  xref C and D)."

28381482

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➶

reach

"Therefore, in light of our findings that both USP26 and SMAD7 are upregulated following stimulation with TGF-beta, we speculated that USP26 might form a complex with SMAD7 following TGF-beta exposure leading to USP26 mediated deubiquitination."

28381482

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➶

sparser

"Having shown that USP26 is induced by RAC1B and that its knockdown decreased SMAD7 protein abundance, it remains to be determined whether in pancreatic carcinoma cells USP26 indeed binds to and deubiquitinates SMAD7, as shown previously in breast cancer and glioma cells [ xref ]."

32545415

---

➶

sparser

"Therefore, in light of our findings that both USP26 and SMAD7 are upregulated following stimulation with TGF‐β, we speculated that USP26 might form a complex with SMAD7 following TGF‐β exposure leading to USP26‐mediated deubiquitination."

28381482

USP26 binds SMAD3, SMAD6, and SMAD7. 1 / 1

| 1

---

➶

sparser

"These data suggest that USP26 can form a stable complex in vivo with SMAD3, SMAD6, and SMAD7."

28381482

RING1 affects USP26

| 4

RING1 binds USP26. 1 / 3

| 1

---

➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

RING1 binds USP26, CBX4, and CBX6. 2 / 2

| 2

---

➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

---

➶

sparser

"USP26 binds to CBX4 and CBX6 in RING1A-independent manner."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

USP26 affects UIMC1

| 5

USP26 inhibits UIMC1.

| 3

USP26 inhibits UIMC1. 3 / 3

| 3

---

➶

reach

"We reasoned that USP26 and USP37 may antagonize the RAP80 dependent sequestration of BRCA1 by removing RNF8 and RNF168 mediated ubiquitylation and thereby promote HR."

26101254

---

➶

reach

"USP26 and USP37 have additionally been shown to impair accumulation of RAP80 and BRCA1 [154]."

32708614

---

➶

reach

"Together, these results suggest that USP26 and USP37 promote the BRCA1 dependent loading of PALB2 and RAD51 by counteracting the repressive impact of RAP80 dependent BRCA1 sequestration and RAP80 dependent inhibition of end-resection during HR."

26101254

USP26 activates UIMC1.

| 2

USP26 activates UIMC1. 2 / 2

| 2

---

➶

reach

"Loss of USP26 or USP37 impairs HR by counteracting RAP80 dependent sequestration of BRCA1."

26101254

---

➶

reach

"Together, this model may explain how USP26 and USP37 limit the repressive impact of RAP80 on HR."

26101254

USP26 affects Neoplasm Invasiveness

| 1 4

USP26 activates Neoplasm Invasiveness.

| 1 2

USP26 activates Neoplasm Invasiveness. 3 / 3

| 1 2

---

➶

reach

"As knockdown of USP26 potently activated the TGF-beta pathway in breast cancer, we investigated whether depletion of USP26 in the TGF-beta-responsive metastatic cell line MDA-MB-231 enhanced cellular motility and invasion."

28381482

---

➶

reach

"USP26 depletion significantly decreased ATC cell proliferation, migration, and invasion."

35397626

---

➶

eidos

"USP26 depletion significantly decreased ATC cell proliferation , migration , and invasion ."

35397626

USP26 inhibits Neoplasm Invasiveness.

| 2

USP26 inhibits Neoplasm Invasiveness. 2 / 2

| 2

---

➶

reach

"Silencing of USP26 significantly enhanced TGF-beta-induced migration and invasion (Fig XREF_FIG A-D)."

28381482

---

➶

reach

"In comparison, stable expression of USP26, but not the catalytically inactive mutant USP26 C/S, attenuated invasion of MDA-MB-231 cells following exposure to TGF-beta (Fig XREF_FIG E-G)."

28381482

CBX4 affects CBX6, and USP26

| 5

USP26 binds CBX4 and CBX6. 5 / 5

| 5

---

➶

sparser

"Since the undifferentiated ESCs expressed CBX7 but no USP26, endogenous interactions between USP26 and CBX4 or CBX6, but not CBX7, were only observed in differentiating ESCs (Fig.  xref )."

28839133

---

➶

sparser

"Taken together, these results suggest that USP26 physically binds to components of the PRC1 complex, including RING1A, CBX4, and CBX6, and the interaction between USP26 and CBX4 or CBX6 is independent of the presence of RING1A."

28839133

---

➶

sparser

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells (Fig.  xref ), suggesting that USP26 and CBX4 or CBX6 interactions are RING1A-independent."

28839133

---

➶

sparser

"However, when USP26 was expressed with either Cbx4 or CBX6, significantly decreased promoter activities of Sox2, Nanog , and Cbx7 were observed (Supplementary Fig.  xref ), suggesting that USP26 interacts with Cbx4 or Cbx6 alone or both in Cbx7 promoter for CBX7 suppression."

28839133

---

➶

sparser

"However, the interaction of USP26 with CBX4 and CBX6 was independent of RING1A. In differentiated cells, USP26 removed K48-linked Ub chains from CBX4 and CBX6, thus stabilizing the proteins and preventing their degradation."

28839133

USP26 affects E7

4 |

USP26 binds E7. 2 / 2

2 |

---

➶

virhostnet

No evidence text available

28786561

---

➶

virhostnet

No evidence text available

28786561

USP26 binds E7. 1 / 1

1 |

---

➶

virhostnet

No evidence text available

28786561

USP26 binds E7. 1 / 1

1 |

---

➶

virhostnet

No evidence text available

28786561

USP26 affects CBX7

| 2

USP26 binds CBX7.

| 1

USP26 binds CBX7. 1 / 3

| 1

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

USP26 decreases the amount of CBX7.

| 1

USP26 decreases the amount of CBX7. 1 / 1

| 1

---

➶

reach

"Our results demonstrate that USP26 can diminish the expression of the Cbx7 gene and inhibit cellular reprogramming."

28839133

SOX2 affects USP26

| 3

SOX2 binds USP26.

| 2

SOX2 binds USP26. 2 / 3

| 2

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

---

➶

reach

"Similarly, during RA induced ESC differentiation, USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 also bound to the Sox2, Nanog, and Cbx7 promoters."

28839133

SOX2 activates USP26.

| 1

SOX2 activates USP26. 1 / 1

| 1

---

➶

reach

"Sox2 and Nanog mRNA levels, but not Oct4, dramatically increased in Cbx4 or Cbx6 knockdown cells, similar to the increased Sox2 and Nanog mRNA levels in Usp26 knockdown cells."

28839133

NANOG affects USP26

| 3

NANOG binds USP26.

| 2

USP26 binds NANOG. 2 / 3

| 2

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

---

➶

reach

"Similarly, during RA induced ESC differentiation, USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 also bound to the Sox2, Nanog, and Cbx7 promoters."

28839133

NANOG activates USP26.

| 1

NANOG activates USP26. 1 / 1

| 1

---

➶

reach

"Sox2 and Nanog mRNA levels, but not Oct4, dramatically increased in Cbx4 or Cbx6 knockdown cells, similar to the increased Sox2 and Nanog mRNA levels in Usp26 knockdown cells."

28839133

E7 affects USP26

4 |

USP26 binds E7. 2 / 2

2 |

---

➶

virhostnet

No evidence text available

28786561

---

➶

virhostnet

No evidence text available

28786561

USP26 binds E7. 1 / 1

1 |

---

➶

virhostnet

No evidence text available

28786561

USP26 binds E7. 1 / 1

1 |

---

➶

virhostnet

No evidence text available

28786561

CBX7 affects USP26

| 2

CBX7 binds USP26.

| 1

USP26 binds CBX7. 1 / 3

| 1

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

CBX7 inhibits USP26.

| 1

CBX7 inhibits USP26. 1 / 1

| 1

---

➶

reach

"To understand how Usp26 expression is regulated, we assessed the promoter binding activity of Usp26 by PRC1 subunits using the ChIP-qPCR assay during RA induced ESC differentiation, and observed that PRC1 components PCGF2 and Cbx7 occupation as well as H2A-ubi1 modifications decreased significantly in Usp26 promoter, thus indicating that CBX7 containing PRC1 complex is a potential repressor of Usp26."

28839133

Reactive oxygen species affects USP26

| 3

Reactive oxygen species inhibits USP26.

| 2

Reactive oxygen species inhibits USP26. 2 / 2

| 2

---

➶

reach

"The increased ROS levels generated by ABT263 can inhibit USP26 activity to ubiquitinate AR/ARv7, and further sensitize PCa cells to Enz treatment."

32235588

---

➶

reach

"In our current study, we screened several AR related USPs, including USP7, USP12, USP14, USP22, and USP26 and found that the USP26 activity was repressed by the induced cellular ROS, which is responsible for AR/ARv7 protein degradation and Enz sensitivity increase by ABT263."

32235588

Reactive oxygen species activates USP26.

| 1

Reactive oxygen species activates USP26. 1 / 1

| 1

---

➶

reach

"An in vitro DUB assay was applied to further detect USP26 activity, and results revealed that ABT263 could significantly decrease USP26 activity, which could be reversed by inhibition of cellular ROS (XREF_FIG H-J)."

32235588

USP26 affects SMAD3

| 1 2

USP26 binds SMAD3. 2 / 2

| 1 1

---

➶

sparser

"As part of this study, we demonstrate that USP26 binds to SMAD3, suggesting that USP26 may also regulate the TGF‐β pathway by enhancing androgen receptor‐mediated repression of SMAD3 transcriptional targets."

28381482

---

➶

reach

"As part of this study, we demonstrate that USP26 binds to SMAD3, suggesting that USP26 may also regulate the TGF-beta pathway by enhancing androgen receptor mediated repression of SMAD3 transcriptional targets."

28381482

USP26 binds SMAD3, SMAD6, and SMAD7. 1 / 1

| 1

---

➶

sparser

"These data suggest that USP26 can form a stable complex in vivo with SMAD3, SMAD6, and SMAD7."

28381482

USP26 affects RAD51

| 3

USP26 activates RAD51. 3 / 3

| 3

---

➶

reach

"Loss of USP26 and USP37 function markedly impairs the assembly of PALB2, RAD51 and efficient HR."

26101254

---

➶

reach

"Together, these results suggest that USP26 and USP37 promote the BRCA1 dependent loading of PALB2 and RAD51 by counteracting the repressive impact of RAP80 dependent BRCA1 sequestration and RAP80 dependent inhibition of end-resection during HR."

26101254

---

➶

reach

"Interestingly, in contrast with initial findings assessing overexpression of these DUBs, knockdown of either USP26 or USP37 impairs accumulation of key HR factors including RAD51 as well as PALB2, CtIP, and RPA [154]."

32708614

USP26 affects POU5F1

| 3

USP26 activates POU5F1.

| 2

Modified USP26 activates POU5F1. 1 / 1

| 1

---

➶

reach

"Overexpression of Usp26 in ESCs led to decreased mRNA levels of Sox2, Nanog, and Oct4 compared with control cells."

28839133

USP26 activates POU5F1. 1 / 1

| 1

---

➶

reach

"Correlative with the Oct4 gene expression data, occupancy at the Oct4 promoter by USP26, CBX4, CBX6, and H2A-ubi1 was low even during USP26 mediated ESC differentiation."

28839133

USP26 decreases the amount of POU5F1.

| 1

USP26 decreases the amount of POU5F1. 1 / 1

| 1

---

➶

reach

"Our results showed that after Usp26 knockdown during Dox induced OSKM mediated MEF reprogramming led to increased mRNA levels of Sox2 and Nanog, but not Oct4, compared with control."

28839133

USP26 affects PALB2

| 3

USP26 activates PALB2. 3 / 3

| 3

---

➶

reach

"Interestingly, in contrast with initial findings assessing overexpression of these DUBs, knockdown of either USP26 or USP37 impairs accumulation of key HR factors including RAD51 as well as PALB2, CtIP, and RPA [154]."

32708614

---

➶

reach

"Together, these results suggest that USP26 and USP37 promote the BRCA1 dependent loading of PALB2 and RAD51 by counteracting the repressive impact of RAP80 dependent BRCA1 sequestration and RAP80 dependent inhibition of end-resection during HR."

26101254

---

➶

reach

"Loss of USP26 and USP37 function markedly impairs the assembly of PALB2, RAD51 and efficient HR."

26101254

SMAD3 affects USP26

| 1 2

USP26 binds SMAD3. 2 / 2

| 1 1

---

➶

sparser

"As part of this study, we demonstrate that USP26 binds to SMAD3, suggesting that USP26 may also regulate the TGF‐β pathway by enhancing androgen receptor‐mediated repression of SMAD3 transcriptional targets."

28381482

---

➶

reach

"As part of this study, we demonstrate that USP26 binds to SMAD3, suggesting that USP26 may also regulate the TGF-beta pathway by enhancing androgen receptor mediated repression of SMAD3 transcriptional targets."

28381482

USP26 binds SMAD3, SMAD6, and SMAD7. 1 / 1

| 1

---

➶

sparser

"These data suggest that USP26 can form a stable complex in vivo with SMAD3, SMAD6, and SMAD7."

28381482

RING1 affects CBX6

| 3

RING1 binds USP26, CBX4, and CBX6. 2 / 2

| 2

---

➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

---

➶

sparser

"USP26 binds to CBX4 and CBX6 in RING1A-independent manner."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

Nuclear receptor affects USP26

| 2

USP26 binds AR and nuclear receptor. 2 / 2

| 2

---

➶

sparser

"USP26 binds to androgen receptor through three nuclear receptor interaction motifs, and knockdown of USP26 leads to decreased receptor activity in LnCaP and HEK293 cells (Dirac and Bernards, xref )."

28381987

---

➶

sparser

"Usp26 binds to AR via nuclear receptor boxes, a hydrophobic motif (LXXLL) found in p160 coactivators."

21820033

ZEB1 affects USP26

2 |

ZEB1 binds USP26. 2 / 2

2 |

---

➶

biogrid

No evidence text available

29119051

---

➶

biogrid

No evidence text available

29119051

USP26 affects transcription, DNA-templated

| 2

USP26 activates transcription, DNA-templated. 2 / 2

| 2

---

➶

reach

"USP26 has been reported to bind to AR through LXXLL and FXXFF motifs to enhance AR deubiquitination and enhance AR downstream transcription [20]."

34545063

---

➶

reach

"In LNCaP cells, Usp26 depletion by siRNA enhances AR dependent transcription, suggesting it acts on a factor that is negatively regulated by ubiquitination (Dirac and Bernards, 2010)."

21820033

USP26 affects nuclear receptor

| 2

USP26 binds AR and nuclear receptor. 2 / 2

| 2

---

➶

sparser

"USP26 binds to androgen receptor through three nuclear receptor interaction motifs, and knockdown of USP26 leads to decreased receptor activity in LnCaP and HEK293 cells (Dirac and Bernards, xref )."

28381987

---

➶

sparser

"Usp26 binds to AR via nuclear receptor boxes, a hydrophobic motif (LXXLL) found in p160 coactivators."

21820033

USP26 affects expression

| 2

USP26 inhibits expression. 2 / 2

| 2

---

➶

sparser

"Overexpression of Usp26 inhibited Sox2 and Nanog gene expression during Dox-induced OSKM-mediated MEF reprogramming (Fig.  xref )."

28839133

---

➶

sparser

"USP26 inhibits expression of pluripotency core genes."

28839133

USP26 affects ZEB1

2 |

ZEB1 binds USP26. 2 / 2

2 |

---

➶

biogrid

No evidence text available

29119051

---

➶

biogrid

No evidence text available

29119051

USP26 affects Ubiquitin

| 2

USP26 inhibits Ubiquitin. 2 / 2

| 2

---

➶

reach

"USP26 or USP37 antagonize ubiquitin dependent spreading of RAP80-BRCA1."

26101254

---

➶

reach

"Therefore, we analyzed whether loss of USP26 increases the levels of SMAD7 Lys48 or Lys63 incorporated ubiquitin chains."

28381482

USP26 affects Thyroid Carcinoma, Anaplastic

| 1 1

USP26 activates Thyroid Carcinoma, Anaplastic. 2 / 2

| 1 1

---

➶

eidos

"USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ ."

35397626

---

➶

reach

"USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ."

35397626

USP26 affects TAFAZZIN

| 2

USP26 increases the amount of TAFAZZIN.

| 1

USP26 increases the amount of TAFAZZIN. 1 / 1

| 1

---

➶

reach

"Depletion of USP26 decreased the TAZ protein level and the expression of TAZ/TEAD target genes in ATC, including CTGF, ANKRD1, and CYR61."

35397626

USP26 activates TAFAZZIN.

| 1

USP26 activates TAFAZZIN. 1 / 1

| 1

---

➶

reach

"USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ."

35397626

USP26 affects SMURF2

| 1 1

USP26 binds SMURF2. 1 / 1

| 1

---

➶

reach

"Indeed, USP26 interacts with both SMURF1 and SMURF2 when in complex with SMAD7 as demonstrated by sequential co-immunoprecipitation (Fig XREF_FIG G and H)."

28381482

USP26 binds SMURF1 and SMURF2. 1 / 1

| 1

---

➶

sparser

"Indeed, USP26 interacts with both SMURF1 and SMURF2 when in complex with SMAD7 as demonstrated by sequential co‐immunoprecipitation (Fig  xref G and H)."

28381482

USP26 affects SMURF1

| 1 1

USP26 binds SMURF1 and SMURF2. 1 / 1

| 1

---

➶

sparser

"Indeed, USP26 interacts with both SMURF1 and SMURF2 when in complex with SMAD7 as demonstrated by sequential co‐immunoprecipitation (Fig  xref G and H)."

28381482

USP26 binds SMURF1. 1 / 1

| 1

---

➶

reach

"Indeed, USP26 interacts with both SMURF1 and SMURF2 when in complex with SMAD7 as demonstrated by sequential co-immunoprecipitation (Fig XREF_FIG G and H)."

28381482

USP26 affects SMAD2

| 2

Modified USP26 increases the amount of SMAD2. 1 / 1

| 1

---

➶

reach

"Overexpression of the catalytically inactive USP26 C/S mutant also enhanced the levels of p-SMAD2 whereas ectopic expression of USP26 slightly diminished the levels of phosphorylated SMAD2 (Fig XREF_FIG B)."

28381482

USP26 increases the amount of SMAD2. 1 / 1

| 1

---

➶

reach

"Conversely, knockdown of USP26 rapidly degrades SMAD7 resulting in TGFbeta receptor stabilization and enhanced levels of p-SMAD2, ultimately enhancing cellular proliferation, invasion, and metastasis [XREF_BIBR]."

33085646

USP26 affects RAP80-BRCA1

| 2

USP26 inhibits RAP80-BRCA1. 2 / 2

| 2

---

➶

reach

"We demonstrate that USP26 and USP37 prevent excessive spreading of RAP80-BRCA1 from DSBs."

26101254

---

➶

reach

"USP26 or USP37 antagonize ubiquitin dependent spreading of RAP80-BRCA1."

26101254

USP26 affects Lys-Ser

| 2

Mutated USP26 activates Lys-Ser. 2 / 2

| 2

---

➶

reach

"Thus, some KS should originate from XY spermatozoa, and paternal USP26 mutations increase the risk of producing KS offspring."

33978233

---

➶

reach

"Consistent with our mouse results, a clinical study shows that some USP26 variations increase the proportion of XY aneuploid spermatozoa in fertile men, and we identified two families with KS offspring wherein the father of the KS patient harbored a USP26 mutated haplotype, further supporting that paternal USP26 mutation can cause KS offspring production."

33978233

USP26 affects H2A-ubi1

| 2

USP26 binds H2A-ubi1. 2 / 2

| 2

---

➶

reach

"ChIP-qPCR analyses revealed the recruitment of Usp26 and H2A-ubi1 to these promoters, suggesting the repression of Sox2, Nanog, and Cbx7 expression by Usp26."

28839133

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

SMURF2 affects USP26

| 1 1

USP26 binds SMURF2. 1 / 1

| 1

---

➶

reach

"Indeed, USP26 interacts with both SMURF1 and SMURF2 when in complex with SMAD7 as demonstrated by sequential co-immunoprecipitation (Fig XREF_FIG G and H)."

28381482

USP26 binds SMURF1 and SMURF2. 1 / 1

| 1

---

➶

sparser

"Indeed, USP26 interacts with both SMURF1 and SMURF2 when in complex with SMAD7 as demonstrated by sequential co‐immunoprecipitation (Fig  xref G and H)."

28381482

SMURF1 affects USP26

| 1 1

USP26 binds SMURF1 and SMURF2. 1 / 1

| 1

---

➶

sparser

"Indeed, USP26 interacts with both SMURF1 and SMURF2 when in complex with SMAD7 as demonstrated by sequential co‐immunoprecipitation (Fig  xref G and H)."

28381482

USP26 binds SMURF1. 1 / 1

| 1

---

➶

reach

"Indeed, USP26 interacts with both SMURF1 and SMURF2 when in complex with SMAD7 as demonstrated by sequential co-immunoprecipitation (Fig XREF_FIG G and H)."

28381482

PRC1 affects CBX6

| 2

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

H2A-ubi1 affects USP26

| 2

USP26 binds H2A-ubi1. 2 / 2

| 2

---

➶

reach

"ChIP-qPCR analyses revealed the recruitment of Usp26 and H2A-ubi1 to these promoters, suggesting the repression of Sox2, Nanog, and Cbx7 expression by Usp26."

28839133

---

➶

reach

"ChIP-qPCR of the promoters of Sox2, Nanog, Oct4, and Cbx7 in Usp26 differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2, Nanog, and Cbx7 promoters, suggesting that promoter binding of these components led to a decrease in pluripotency gene expression."

28839133

CBX6 affects PRC1

| 2

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

CBX4 affects CBX6, RING1, and USP26

| 2

RING1 binds USP26, CBX4, and CBX6. 2 / 2

| 2

---

➶

sparser

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6 (Fig.  xref )."

28839133

---

➶

sparser

"USP26 binds to CBX4 and CBX6 in RING1A-independent manner."

28839133

CBX4 affects CBX6, CBX7, NANOG, SOX2, and USP26

| 2

SOX2 binds USP26, CBX4, CBX6, CBX7, and NANOG. 2 / 2

| 2

---

➶

sparser

"ChIP–qPCR of the promoters of Sox2 , Nanog , Oct4 , and Cbx7 in Usp26 -differentiated ESCs on day 6 revealed binding of USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 to the Sox2 , Nanog , and Cbx7 promoters (Fig.  xref ), suggesting that promoter-binding of these components led to a decrease in pluripotency gene expression (Fig.  xref )."

28839133

---

➶

sparser

"Similarly, during RA-induced ESC differentiation, USP26, CBX4, CBX6, H2A-ubi1, and H3K27me3 also bound to the Sox2 , Nanog , and Cbx7 promoters (Supplementary Fig. xref a)."

28839133

AR affects nuclear receptor

| 2

USP26 binds AR and nuclear receptor. 2 / 2

| 2

---

➶

sparser

"USP26 binds to androgen receptor through three nuclear receptor interaction motifs, and knockdown of USP26 leads to decreased receptor activity in LnCaP and HEK293 cells (Dirac and Bernards, xref )."

28381987

---

➶

sparser

"Usp26 binds to AR via nuclear receptor boxes, a hydrophobic motif (LXXLL) found in p160 coactivators."

21820033

Hairpins affects USP26

| 1

Hairpins activates USP26. 1 / 1

| 1

---

➶

reach

"About 2x10 5 MDA-MB-231 cells expressing either control vector, or hairpins targeting USP26 were seeded per well in a six-well plate."

28381482

Cadmium dichloride affects USP26

1 |

Cadmium dichloride increases the amount of USP26. 1 / 1

1 |

---

➶

ctd

No evidence text available

20061341

ZHX2 affects USP26

1 |

ZHX2 decreases the amount of USP26. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

ZFP42 affects USP26

| 1

ZFP42 activates USP26. 1 / 1

| 1

---

➶

reach

"RNF12 relieved REX1-mediated repression of Usp26 , leading to an increase in USP26 abundance and the formation of RNF12-USP26 complexes."

35857630

USP37 affects USP26

| 1

E3_Ub_ligase binds USP26 and USP37. 1 / 1

| 1

---

➶

sparser

"Thus, our results suggest that USP26 and USP37 are able to bind to chromatin modified by RNF8/RNF168 and reverse ubiquitylation induced by these E3 ligases at DSBs."

26101254

USP26 affects retinoic acid

| 1

USP26 activates retinoic acid. 1 / 1

| 1

---

➶

reach

"Conversely, lesser extent of CBX7 protein binding to the promoters of Cbx4 and Cbx6 is observed during Usp26 mediated ESC differentiation and RA induced ESC differentiation."

28839133

USP26 affects polyubiquitin chains

| 1

USP26 inhibits polyubiquitin chains. 1 / 1

| 1

---

➶

reach

"Interestingly, RAP80 's access to polyubiquitin chains assembled by RNF8 and RNF168 is regulated by HR promoting factors such as RNF169, which competes with RAP80 for binding sites on polyubiquitin [XREF_BIBR], and the DUBs USP26 and USP37, which degrade polyubiquitin chains to reduce RAP80 accumulation [XREF_BIBR]."

28681078

USP26 affects polyubiquitin chain

| 1

USP26 inhibits polyubiquitin chain. 1 / 1

| 1

---

➶

reach

"Importantly, ectopic expression of USP26 completely abolished polyubiquitin chain linkages associated with SMAD7, while monoubiquitinated isoforms were still detected (Fig XREF_FIG E)."

28381482

USP26 affects pluripotency core genes

| 1

USP26 decreases the amount of pluripotency core genes. 1 / 1

| 1

---

➶

reach

"USP26 inhibits expression of pluripotency core genes."

28839133

USP26 affects physiological events

| 1

USP26 inhibits physiological events. 1 / 1

| 1

---

➶

eidos

"Furthermore , the USP26 mimic plasmid transfection enhanced these activities , while , conversely , USP26 and AR inhibitor plasmid transfection suppressed the physiological events ."

33064378

USP26 affects osteogenic differentiation

| 1

USP26 activates osteogenic differentiation. 1 / 1

| 1

---

➶

eidos

"USP26 promotes the osteogenic differentiation of MSCs by stabilizing beta-catenin and impairs the osteoclastic differentiation of bone myelomonocytes ( BMMs ) by stabilizing inhibitors of NF-kappaBalpha ( Li et al ., 2022 ) ."

36340031

USP26 affects osteoclastic differentiation bone myelomonocytes

| 1

USP26 inhibits osteoclastic differentiation bone myelomonocytes. 1 / 1

| 1

---

➶

eidos

"Mechanistically , USP26 stabilizes beta-catenin to promote the osteogenic activity of mesenchymal cells ( MSCs ) and impairs the osteoclastic differentiation of bone myelomonocytes ( BMMs ) by stabilizing inhibitors of NF-kappaBalpha ( IkappaBalpha ) ."

35091692

USP26 affects migration

| 1

USP26 activates migration. 1 / 1

| 1

---

➶

eidos

"USP26 depletion significantly decreased ATC cell proliferation , migration , and invasion ."

35397626

USP26 affects miR-203

| 1

USP26 activates miR-203. 1 / 1

| 1

---

➶

reach

"TargetScan was used for in situ prediction of miR-203 targets and in vitro heterologous reporter assays using the wild-type and miR-203 seed mutant of the 3 ' Untranslated region (UTR) of USP26 were used to investigate whether USP26 is a target of miR-203."

32760222

USP26 affects maleate(2-)

| 1

USP26 activates maleate(2-). 1 / 1

| 1

---

➶

reach

"Novel Mutations in X Linked, USP26 Induced Asthenoteratozoospermia and Male Infertility."

34202084

USP26 affects drosophila mothers

| 1

USP26 activates drosophila mothers. 1 / 1

| 1

---

➶

eidos

"Low levels of USP26 degrade drosophila mothers against decapentaplegic protein 7 ( SMAD7 ) and stabilize TGFbeta , while high levels of USP26 stabilize SMAD7 by deubiquitylation and form a complex with SMAD ubiquitylation regulatory factor 2 ( SMURF2 ) , which degrades the TGF-beta receptor by ubiquitylation [ 34 ] ."

33925279

USP26 affects complex assembly

| 1

USP26 inhibits complex assembly. 1 / 1

| 1

---

➶

reach

"These data suggest that USP26 and USP37 limit the magnitude of BRCA1-A complex assembly in DSB neighboring chromatin by counteracting RNF168 mediated H2A ubiquitylation."

26101254

USP26 affects cell

| 1

USP26 activates cell. 1 / 1

| 1

---

➶

eidos

"USP26 depletion significantly decreased ATC cell proliferation , migration , and invasion ."

35397626

USP26 affects cell population proliferation

| 1

USP26 activates cell population proliferation. 1 / 1

| 1

---

➶

reach

"USP26 depletion significantly decreased ATC cell proliferation, migration, and invasion."

35397626

USP26 affects bone regeneration

| 1

USP26 activates bone regeneration. 1 / 1

| 1

---

➶

reach

"Gain-of-function experiments revealed that Usp26 supplementation significantly increased bone regeneration in bone defects in aged mice and decreased bone loss resulting from ovariectomy."

35091692

USP26 affects biological_process

| 1

USP26 activates biological_process. 1 / 1

| 1

---

➶

eidos

"Moreover , the results from co-immunoprecipitation ( CO-IP ) , immunofluorescence and western blot assays showed that the physiological process due to USP26 interacted with AR and influenced AR deubiquitination , thus upregulating the proteins CCND1 and SPATA46 - which are associated with cell cycle progression and spermatogenesis - as well as decreasing the expression of TP73 ."

33064378

USP26 affects activity

| 1

USP26 inhibits activity. 1 / 1

| 1

---

➶

sparser

"Taken together, these data indicate that USP26 inhibits TGF‐β pathway activity by limiting Lys48 ubiquitin‐mediated degradation of SMAD7 consequently resulting in enhanced ubiquitylation and degradation of the TβR complex."

28381482

USP26 affects Wnt

| 1

USP26 activates Wnt. 1 / 1

| 1

---

➶

eidos

"USP26 can activate Wnt signaling by stabilizing p-catenin ."

36340031

USP26 affects USP37

| 1

E3_Ub_ligase binds USP26 and USP37. 1 / 1

| 1

---

➶

sparser

"Thus, our results suggest that USP26 and USP37 are able to bind to chromatin modified by RNF8/RNF168 and reverse ubiquitylation induced by these E3 ligases at DSBs."

26101254

USP26 affects USP26

| 1

USP26 decreases the amount of USP26. 1 / 1

| 1

---

➶

reach

"We isolated the two hairpin vectors from the USP26 DUB pool, which had previously been demonstrated to most effectively inhibit USP26 expression and tested their ability to knockdown USP26 24."

28381482

USP26 affects USP17L7

1 |

USP26 binds USP17L7. 1 / 1

1 |

---

➶

biogrid

No evidence text available

19615732

USP26 affects UBE2L3

1 |

UBE2L3 binds USP26. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22939629

USP26 affects TGF-beta1-mediated breast cancer

| 1

USP26 inhibits TGF-beta1-mediated breast cancer. 1 / 1

| 1

---

➶

eidos

"Novel regulators of SMAD7 , including OTU domain-containing protein 1 ( OTUD1 ) and ubiquitin-specific protease 26 ( USP26 ) , attenuate TGF-beta1-mediated aggressive phenotypes in breast cancer ."

33823905

USP26 affects TEAD

| 1

USP26 increases the amount of TEAD. 1 / 1

| 1

---

➶

reach

"Depletion of USP26 decreased the TAZ protein level and the expression of TAZ/TEAD target genes in ATC, including CTGF, ANKRD1, and CYR61."

35397626

USP26 affects TBCB

| 1

USP26 binds TBCB and AR. 1 / 1

| 1

---

➶

sparser

"Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity."

20501646

USP26 affects TAZ protein

| 1

USP26 activates TAZ protein. 1 / 1

| 1

---

➶

eidos

"Depletion of USP26 decreased the TAZ protein level and the expression of TAZ / TEAD target genes in ATC , including CTGF , ANKRD1 , and CYR61 ."

35397626

USP26 affects TAZ TEAD target including CTGF ANKRD1 CYR61

| 1

USP26 activates TAZ TEAD target including CTGF ANKRD1 CYR61. 1 / 1

| 1

---

➶

eidos

"Depletion of USP26 decreased the TAZ protein level and the expression of TAZ / TEAD target genes in ATC , including CTGF , ANKRD1 , and CYR61 ."

35397626

USP26 affects SMAD7 deubiquitination

| 1

USP26 activates SMAD7 deubiquitination. 1 / 1

| 1

---

➶

eidos

"Examples include ubiquitin-specific protease 10 ( USP10 ) , which can act on SMAD4 to make it deubiquitinated and stable , further promoting TGF-beta signaling [ 138 ] , and USP26 , which promotes SMAD7 deubiquitination , thereby amplifying the inhibitory effect of SMAD7 and strengthening the inhibition of the TGF-beta signaling pathway [ 139 ] ."

34335834

USP26 affects SMAD6

| 1

USP26 binds SMAD3, SMAD6, and SMAD7. 1 / 1

| 1

---

➶

sparser

"These data suggest that USP26 can form a stable complex in vivo with SMAD3, SMAD6, and SMAD7."

28381482

USP26 affects SMAD2_3

| 1

USP26 leads to the phosphorylation of SMAD2_3. 1 / 1

| 1

---

➶

reach

"As USP26 appears to mediate SMAD2/3 phosphorylation and downstream TGF-beta activity, we reasoned that USP26 may function through the canonical TGF-beta pathway."

28381482

USP26 affects RP23-94N18.7

1 |

USP26 binds RP23-94N18.7. 1 / 1

1 |

---

➶

biogrid

No evidence text available

28839133

USP26 affects RP23-458A23.2

1 |

USP26 binds RP23-458A23.2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

28839133

USP26 affects RNF8/168

| 1

USP26 inhibits RNF8/168. 1 / 1

| 1

---

➶

reach

"Given that USP26 and USP37 are able to reverse RNF8/168 mediated ubiquitylation and promote HR, these enzymes would be ideal candidates to facilitate the repositioning of ubiquitylated substrates away from the DSB."

26101254

USP26 affects RNF168

| 1

USP26 activates RNF168. 1 / 1

| 1

---

➶

reach

"Interestingly, the DUBs USP26 and USP27 were found to modulate RNF168 mediated protein ubiquitylation at DSB sites, preventing excessive spreading of RAP80-BRCA1, promoting association of BRCA1 with P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

29499138

USP26 affects RNF12-USP26

| 1

USP26 inhibits RNF12-USP26. 1 / 1

| 1

---

➶

reach

"Furthermore, this RNF12-USP26 axis was disrupted by RLIM and USP26 variants found in TOKAS and infertility patients, respectively."

35857630

USP26 affects RING1A

| 1

USP26 binds RING1A. 1 / 1

| 1

---

➶

reach

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6."

28839133

USP26 affects PCGF1

| 1

USP26 binds PCGF1. 1 / 1

| 1

---

➶

sparser

"Components of the PRC1.2 complex including RING1A, PCGF2, CBX4, CBX6, and CBX7 interacted with USP26, but components of other PRC1 families, such as RING1B (all PRC1s), RYBP (all PRC1s), PCGF1 (PRC1.1), BMI1 (PRC1.4; Fig.  xref ) as well as KDM2B (PRC1.1) and PHC1 (PRC1.4; Supplementary Fig. xref a), did not interact with USP26."

28839133

USP26 affects Neoplasm Metastasis

| 1

USP26 activates Neoplasm Metastasis. 1 / 1

| 1

---

➶

reach

"USP26 promotes esophageal squamous cell carcinoma metastasis through stabilizing Snail."

30763716

USP26 affects Mice

| 1

USP26 activates Mice. 1 / 1

| 1

---

➶

reach

"Gain-of-function experiments revealed that Usp26 supplementation significantly increased bone regeneration in bone defects in aged mice and decreased bone loss resulting from ovariectomy."

35091692

USP26 affects H2AC17

1 |

USP26 deubiquitinates H2AC17. 1 / 1

1 |

---

➶

ubibrowser

"Review"

28031783

USP26 affects FlaG

| 1

USP26 binds FlaG. 1 / 1

| 1

---

➶

sparser

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells (Fig.  xref ), suggesting that USP26 and CBX4 or CBX6 interactions are RING1A-independent."

28839133

USP26 affects E7BBT6

1 |

USP26 binds E7BBT6. 1 / 1

1 |

---

➶

virhostnet

No evidence text available

28786561

USP26 affects E3_Ub_ligase

| 1

E3_Ub_ligase binds USP26 and USP37. 1 / 1

| 1

---

➶

sparser

"Thus, our results suggest that USP26 and USP37 are able to bind to chromatin modified by RNF8/RNF168 and reverse ubiquitylation induced by these E3 ligases at DSBs."

26101254

USP26 affects DSB repair

| 1

USP26 activates DSB repair. 1 / 1

| 1

---

➶

reach

"Loss of USP26 or USP37 impairs DSB repair."

26101254

USP26 affects CDKN2A

1 |

USP26 binds CDKN2A. 1 / 1

1 |

---

➶

biogrid

No evidence text available

17955473

USP26 affects BRCA1-A

| 1

USP26 inhibits BRCA1-A. 1 / 1

| 1

---

➶

reach

"These data suggest that USP26 and USP37 limit the magnitude of BRCA1-A complex assembly in DSB neighboring chromatin by counteracting RNF168 mediated H2A ubiquitylation."

26101254

USP26 affects BRCA1-A complex

| 1

USP26 decreases the amount of BRCA1-A complex. 1 / 1

| 1

---

➶

reach

"Since depletion of USP26 or USP37 also resulted in defective CtIP recruitment (DNA-end resection), reduced RAD51 foci formation (nucleofilament formation) and inefficient HR, it was suggested that USP[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

28764946

USP26 affects Asthenozoospermia

| 1

USP26 inhibits Asthenozoospermia. 1 / 1

| 1

---

➶

eidos

"These findings suggest that a deficiency in USP26 can cause severe asthenoteratozoospermia , mainly manifesting as multiple malformations in both the sperm heads and flagella ."

34202084

USP26 affects Ala-Pro

| 1

USP26 inhibits Ala-Pro. 1 / 1

| 1

---

➶

reach

"In contrast, the overexpression of Usp26 decreased the number of AP + colonies, while overexpression of Usp20 increased the number of AP + colonies."

28839133

USP26 affects ATM

| 1

USP26 activates ATM. 1 / 1

| 1

---

➶

reach

"USP26 depletion significantly decreased ATC cell proliferation, migration, and invasion."

35397626

USP17L7 affects USP26

1 |

USP26 binds USP17L7. 1 / 1

1 |

---

➶

biogrid

No evidence text available

19615732

UBE2L3 affects USP26

1 |

UBE2L3 binds USP26. 1 / 1

1 |

---

➶

biogrid

No evidence text available

22939629

TBCB affects USP26

| 1

USP26 binds TBCB and AR. 1 / 1

| 1

---

➶

sparser

"Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity."

20501646

SMURF2 affects SMURF1

| 1

USP26 binds SMURF1 and SMURF2. 1 / 1

| 1

---

➶

sparser

"Indeed, USP26 interacts with both SMURF1 and SMURF2 when in complex with SMAD7 as demonstrated by sequential co‐immunoprecipitation (Fig  xref G and H)."

28381482

SMAD7 affects SMAD6

| 1

USP26 binds SMAD3, SMAD6, and SMAD7. 1 / 1

| 1

---

➶

sparser

"These data suggest that USP26 can form a stable complex in vivo with SMAD3, SMAD6, and SMAD7."

28381482

RP23-94N18.7 affects USP26

1 |

USP26 binds RP23-94N18.7. 1 / 1

1 |

---

➶

biogrid

No evidence text available

28839133

RP23-458A23.2 affects USP26

1 |

USP26 binds RP23-458A23.2. 1 / 1

1 |

---

➶

biogrid

No evidence text available

28839133

RNF168 affects USP26

| 1

RNF168 ubiquitinates USP26. 1 / 1

| 1

---

➶

sparser

"USP26 and USP37 reverse RNF168-induced ubiquitylation at DSBs."

26101254

RING1A affects USP26

| 1

USP26 binds RING1A. 1 / 1

| 1

---

➶

reach

"However, in CBX4 or CBX6 knockout 293T cells, USP26 did not interact with RING1A, suggesting that USP26 and RING1A interactions are dependent on the presence of CBX4 or CBX6."

28839133

RING1 affects PRC1

| 1

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

PCGF1 affects USP26

| 1

USP26 binds PCGF1. 1 / 1

| 1

---

➶

sparser

"Components of the PRC1.2 complex including RING1A, PCGF2, CBX4, CBX6, and CBX7 interacted with USP26, but components of other PRC1 families, such as RING1B (all PRC1s), RYBP (all PRC1s), PCGF1 (PRC1.1), BMI1 (PRC1.4; Fig.  xref ) as well as KDM2B (PRC1.1) and PHC1 (PRC1.4; Supplementary Fig. xref a), did not interact with USP26."

28839133

USP26 is modified

| 1

USP26 is ubiquitinated. 1 / 1

| 1

---

➶

sparser

"In a cell-free system we asked whether USP26 can be ubiquitinated by HeLa extract."

27810359

Hemagglutinins affects USP26

| 1

Hemagglutinins activates USP26. 1 / 1

| 1

---

➶

reach

"To this end, we co-transfected HEK293T cells with expression plasmids encoding a constitutively active TbetaR (TRICA) and HA tagged ubiquitin in the presence of shRNA vectors targeting USP26."

28381482

GATA6 affects USP26

1 |

GATA6 decreases the amount of USP26. 1 / 1

1 |

---

➶

biopax:msigdb

No evidence text available

FlaG affects USP26

| 1

USP26 binds FlaG. 1 / 1

| 1

---

➶

sparser

"IP experiments showed binding of FLAG-USP26 and CBX4 or CBX6 in RING1A KO 293T cells (Fig.  xref ), suggesting that USP26 and CBX4 or CBX6 interactions are RING1A-independent."

28839133

EXTRACT affects USP26

| 1

EXTRACT ubiquitinates USP26. 1 / 1

| 1

---

➶

trips

"In a cell-free system we asked whether USP26 can be ubiquitinated by HeLa extract."

27810359

E7BBT6 affects USP26

1 |

USP26 binds E7BBT6. 1 / 1

1 |

---

➶

virhostnet

No evidence text available

28786561

E3_Ub_ligase affects USP37

| 1

E3_Ub_ligase binds USP26 and USP37. 1 / 1

| 1

---

➶

sparser

"Thus, our results suggest that USP26 and USP37 are able to bind to chromatin modified by RNF8/RNF168 and reverse ubiquitylation induced by these E3 ligases at DSBs."

26101254

CDKN2A affects USP26

1 |

USP26 binds CDKN2A. 1 / 1

1 |

---

➶

biogrid

No evidence text available

17955473

CBX4 affects CBX6, PRC1, and USP26

| 1

USP26 binds CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"We further identified that USP26 directly bound to CBX4 and CBX6 proteins and other components of the PRC1.2 complex, including RING1A, PCGF2, and CBX7."

28839133

CBX4 affects CBX6, PRC1, RING1, and USP26

| 1

RING1 binds USP26, CBX4, CBX6, and PRC1. 1 / 1

| 1

---

➶

sparser

"To determine whether USP26 interacts with the PRC1 components RING1A, CBX4, and CBX6 independent of each other, we generated RING1A, CBX4, or CBX6 knockout 293T cells using CRISPR/Cas9 technology (Supplementary Fig. xref c, d)."

28839133

AR affects TBCB, and USP26

| 1

USP26 binds TBCB and AR. 1 / 1

| 1

---

➶

sparser

"Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity."

20501646

ABT263 affects USP26

| 1

ABT263 inhibits USP26. 1 / 1

| 1

---

➶

reach

"An in vitro DUB assay was applied to further detect USP26 activity, and results revealed that ABT263 could significantly decrease USP26 activity, which could be reversed by inhibition of cellular ROS (XREF_FIG H-J)."

32235588

2,3',4,4',5-pentachlorobiphenyl affects USP26

1 |

2,3',4,4',5-pentachlorobiphenyl increases the amount of USP26. 1 / 1

1 |

---

➶

ctd

No evidence text available

31388691