IndraLab

"Knowing that Usp16 regulates the localization of Plk1 on the kinetochores by deubiquitinating Plk1, we wanted to know whether Plk1 positively regulates its own kinetochore localization by phosphorylating and activating Usp16."

"Knowing that Usp16 regulates the localization of Plk1 on the kinetochores by deubiquitinating Plk1, we wanted to know whether Plk1 positively regulates its own kinetochore localization by phosphorylating and activating Usp16."

"To identify the regulatory elements in the USP16 promotor region, a series of deletion fragments within p USP16 -A was generated (Fig.  xref a)."

"Collectively, our results strongly suggest that CDK1 promotes the interaction between Plk1 and Usp16 and enhances the phosphorylation of Usp16 by Plk1."

"CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase’s kinetochore localization and promote proper chromosome alignment in mitosis."

"RT-PCR with Usp16 specific primers confirmed equivalent mRNA expression, suggesting that Usp16 phosphorylation promotes protein degradation."

"Importantly, the combined use of CDK1 and Plk1 enhanced the phosphorylation of the peptide aa 150–600 (Fig. 3 B), which is consistent with our early finding that CDK1 is the priming kinase for Plk1 in Usp16 phosphorylation."

"Plk1 phosphorylates and activates Usp16."

"Next, we set out to investigate the function of Usp16 phosphorylation by Plk1."

"To determine the functional promoter region of the human USP16 gene, we cloned a 2324 bp 5′ flanking region of the USP16 gene into a promoter-lacking vector pGL4.10 to generate p USP16 -A (− 1856 bp to + 468 bp) plasmid."

"Therefore, these studies confirm that Ubp-M is phosphorylated at S552 and identify CDK1 as the enzyme responsible for the phosphorylation."

"Future studies will be required to confirm whether TTK-dependent phosphorylation of Usp16 S552 plays a similar role in regulating Plk1 to maintain proper SAC function."

No evidence text available

No evidence text available

No evidence text available

"Mass spectrometry analysis confirmed Ubp-M is phosphorylated at serine 552, and in vitro and in vivo assays demonstrated that CDK1/cyclin B kinase is responsible for Ubp-M S552P."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

"By sequence analysis, we found three (S330, S386, and S486) potential Plk1 phosphorylation sites on Usp16 (Fig. S2 C). In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig. S2 D). MS of peptides derived from proteins isolated from HeLa cells revealed two phosphorylation sites, S330 and S386 (Fig."

"According to our findings, USP16 methylation is increased in breast metastatic disease, in agreement with findings in hepatocellular carcinoma [ xref ]."

"Plk1 phosphorylates and activates Usp16."

"In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig. S2 D)."

"Collectively, our results strongly suggest that CDK1 promotes the interaction between Plk1 and Usp16 and enhances the phosphorylation of Usp16 by Plk1."

"CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase’s kinetochore localization and promote proper chromosome alignment in mitosis."

"Collectively, our results strongly suggest that CDK1 promotes the interaction between Plk1 and Usp16 and enhances the phosphorylation of Usp16 by Plk1."

"We found that the level of ubiquitinated histone H2A (ubH2A) was high in interphase and low in mitotic HeLa cells (Fig. S3, C–E), suggesting that Plk1 phosphorylates and activates Usp16."

"We found that the level of ubiquitinated histone H2A (ubH2A) was high in interphase and low in mitotic HeLa cells, suggesting that Plk1 phosphorylates and activates Usp16."

"Collectively, our results strongly suggest that CDK1 promotes the interaction between Plk1 and Usp16 and enhances the phosphorylation of Usp16 by Plk1."

"These results strongly suggest that Plk1 phosphorylates and activates Usp16, but the exact molecular mechanism of the activation is not clear at the moment."

"Plk1 phosphorylates and activates Usp16."

No evidence text available

"In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig."

"By sequence analysis, we found three (S330, S386, and S486) potential Plk1 phosphorylation sites on Usp16 (Fig."

No evidence text available

No evidence text available

"Next, we treated HeLa cells with CDK1 inhibitor RO3306 and observed a significant reduction in Plk1–Usp16 interaction ( xref )."

"Because Usp16 interacts with Plk1, we suspected that it might deubiquitinate Plk1."

"Collectively, our results strongly suggest that CDK1 promotes the interaction between Plk1 and Usp16 and enhances the phosphorylation of Usp16 by Plk1."

"Collectively, our results strongly suggest that CDK1 promotes the interaction between Plk1 and Usp16 and enhances the phosphorylation of Usp16 by Plk1."

"These data strongly suggest that the phosphorylation of S552 by CDK1 promotes Plk1–Usp16 interaction."

No evidence text available

"Recently, CDK1 dependent phosphorylation of Usp16 on S552 was shown to promote an interaction between Usp16 and Plk1."

No evidence text available

"Because Usp16 is phosphorylated by CDK1 ( xref ; xref ), we speculated that CDK1 might serve as a priming kinase regulating Plk1–Usp16 interaction in a way similar to other cases ( xref ; xref )."

"To identify any deubiquitylases that may deubiquitinate Plk1 in early mitosis, we performed reciprocal coimmunoprecipitation (coIP) assays and found that Usp16 specifically interacted with Plk1 in nocodazole arrested prometaphase HeLa cells (XREF_FIG)."

"We found that the level of ubiquitinated histone H2A (ubH2A) was high in interphase and low in mitotic HeLa cells (Fig. S3, C–E), suggesting that Plk1 phosphorylates and activates Usp16."

"CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase’s kinetochore localization and promote proper chromosome alignment in mitosis."

"Because Usp16 deubiquitinates Plk1, we wondered whether Plk1 mediated Usp16 activation would also enhance the deubiquitination of Plk1 itself."

"These results suggest that Plk1 activates Usp16, which, in turn, deubiquitinates Plk1 itself."

"Plk1 phosphorylates and activates Usp16."

"These results suggest that Plk1 activates Usp16, which, in turn, deubiquitinates Plk1 itself."

"These results strongly suggest that Plk1 phosphorylates and activates Usp16, but the exact molecular mechanism of the activation is not clear at the moment."

"Next, we treated HeLa cells with CDK1 inhibitor RO3306 and observed a significant reduction in Plk1–Usp16 interaction ( xref )."

"Because Usp16 interacts with Plk1, we suspected that it might deubiquitinate Plk1."

"Collectively, our results strongly suggest that CDK1 promotes the interaction between Plk1 and Usp16 and enhances the phosphorylation of Usp16 by Plk1."

"Collectively, our results strongly suggest that CDK1 promotes the interaction between Plk1 and Usp16 and enhances the phosphorylation of Usp16 by Plk1."

"These data strongly suggest that the phosphorylation of S552 by CDK1 promotes Plk1–Usp16 interaction."

No evidence text available

"Recently, CDK1 dependent phosphorylation of Usp16 on S552 was shown to promote an interaction between Usp16 and Plk1."

No evidence text available

"Because Usp16 is phosphorylated by CDK1 ( xref ; xref ), we speculated that CDK1 might serve as a priming kinase regulating Plk1–Usp16 interaction in a way similar to other cases ( xref ; xref )."

"To identify any deubiquitylases that may deubiquitinate Plk1 in early mitosis, we performed reciprocal coimmunoprecipitation (coIP) assays and found that Usp16 specifically interacted with Plk1 in nocodazole arrested prometaphase HeLa cells (XREF_FIG)."

"ubiquitinspecific peptidase 16 (Usp16) was identified as a PLK1 interacting protein in a co-immunoprecipitation (co-IP) assay in a PBD-dependent manner"

"In this study, we show that ubiquitin specific peptidase 16 (Usp16) is a novel substrate for Plk1, and sequential phosphorylation by CDK1 and Plk1 activates Usp16, which, in turn, deubiquitinates Plk1 and promotes the recruitment of Plk1 to, and its retention on, the kinetochores for proper chromosome alignment."

"Collectively, these results suggest that Plk1 is ubiquitinated by CUL3 based ubiquitin ligase in vivo, and the ubiquitination of Plk1 could be reversed by Usp16, which interacts with Plk1 in a PBD dependent manner in early mitosis."

"Usp16 interacts with and deubiquitinates Plk1."

"Because Usp16 deubiquitinates Plk1, we wondered whether Plk1 mediated Usp16 activation would also enhance the deubiquitination of Plk1 itself."

"When Usp16 was knocked down by siRNA, we found that the ladder pattern bands above the main Plk1 band were enhanced, confirming our previous speculation that Usp16 might deubiquitinate Plk1 (XREF_FIG)."

"CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase 's kinetochore localization and promote proper chromosome alignment in mitosis."

"Usp16 deubiquitinates Plk1, resulting in an enhanced interaction with kinetochore localized proteins such as BubR1, and thereby retains Plk1 on the kinetochores to promote proper chromosome alignment in early mitosis."

"Thus, our data unveil a unique mechanism by which Usp16 promotes the localization and maintenance of Plk1 on the kinetochores for proper chromosome alignment."

"We found that, whereas the kinetochore localization of BubR1 was unchanged in both the control and Usp16 knockdown HeLa cells, knockdown of Usp16 in the cells reduced the amount of Plk1 localized on the kinetochores (XREF_FIG) and the binding between Plk1 and BubR1 (XREF_FIG)."

"It was found that the WT and 3E, but not 3A, Usp16 could restore the level of kinetochore localized Plk1, which was initially reduced by Usp16 knockdown (XREF_FIG)."

"Because the kinetochore localization of Plk1 is necessary for kinetochore-microtubule attachment and subsequent chromosome alignment, we speculated that suppression of Usp16, i.e., reducing the amount of Plk1 on the kinetochores, would delay the chromosome alignment and anaphase onset."

"Recently, CDK1 dependent phosphorylation of Usp16 on S552 was shown to promote an interaction between Usp16 and Plk1."

No evidence text available

"Ubp-M serine 552 phosphorylation by cyclin-dependent kinase 1 regulates cell cycle progression."

"Here, we report that cyclin-dependent kinase 1 (CDK1) phosphorylates the histone H2A deubiquitinase Ubp-M at serine 552 (S552P), and, importantly, this phosphorylation is required for cell cycle progression."

"Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression."

"Cdk1 phosphorylates Usp16 and enhances its binding to Plk1."

"Because Usp16 is phosphorylated by CDK1 ( xref ; xref ), we speculated that CDK1 might serve as a priming kinase regulating Plk1–Usp16 interaction in a way similar to other cases ( xref ; xref )."

"Because Usp16 is phosphorylated by CDK1, we speculated that CDK1 might serve as a priming kinase regulating Plk1-Usp16 interaction in a way similar to other cases."

"CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase’s kinetochore localization and promote proper chromosome alignment in mitosis."

"Cdk1 phosphorylates Usp16 and enhances its binding to Plk1."

"Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression."

"CDK1 and Plk1 sequentially phosphorylate and activate Usp16, which in turn deubiquitinates Plk1 to maintain the kinase’s kinetochore localization and promote proper chromosome alignment in mitosis."

No evidence text available

No evidence text available

No evidence text available

"Depletion of the NBD disrupted the interaction of USP16 with both IKKbeta and IKKalpha (XREF_FIG), which further suggests that USP16 and NEMO may competitively bind to IKKbeta and IKKalpha."

"Co-IP indicated that the UBP14 domain is indispensable for USP16 binding to IKKbeta (XREF_FIG)."

"Under TNF-α stimulation, coimmunoprecipitation (co-IP) assays demonstrated that USP16 physically associated with IKKβ but not with p105 or IκBα in cotransfected HEK293T cells ( xref )."

"Under TNF-alpha stimulation, coimmunoprecipitation (co-IP) assays demonstrated that USP16 physically associated with IKKbeta but not with p105 or IkappaBalpha in cotransfected HEK293T cells (XREF_FIG)."

"In transfected HEK293T cells, the results of co-IP revealed that the association between IKKbeta and USP16 was dependent on the NBD of IKKbeta (XREF_FIG)."

"USP16 selectively interacts with IKKbeta and IKKalpha."

"To further confirm the interaction between endogenous USP16 and IKKbeta, we generated USP16 fl mice and crossed them with Lyz2-Cre mice to delete USP16 in myeloid cells, producing myeloid cell specific USP16-KO (USP16 MKO) mice."

"Co-IP indicated that the UBP14 domain is indispensable for USP16 binding to IKKβ ( xref )."

"By comparison with NEMO, we identified five conserved amino acids that are important for binding between USP16 and IKKbeta, as suggested by the disappearance of the signal upon deletion of the sequence (XREF_FIG)."

"To further confirm the interaction between endogenous USP16 and IKKβ, we generated USP16 fl mice and crossed them with Lyz2 -Cre mice to delete USP16 in myeloid cells, producing myeloid cell–specific USP16-KO (USP16 MKO ) mice (fig."

"USP16 selectively interacts with IKKβ and IKKα."

"Depletion of the NBD disrupted the interaction of USP16 with both IKKβ and IKKα ( xref ), which further suggests that USP16 and NEMO may competitively bind to IKKβ and IKKα."

"Depletion of the NBD disrupted the interaction of USP16 with both IKKβ and IKKα ( xref ), which further suggests that USP16 and NEMO may competitively bind to IKKβ and IKKα."

"These data establish USP16 and USP16 mediated IKKbeta ubiquitination as a novel regulatory mechanism of NF-kappaB signaling and intestinal tumorigenesis and suggest an important role of USP16 in colitis related CRC pathogenesis."

"This observation raised a critical question regarding whether USP16 directly regulates IKKbeta activity or p105 phosphorylation."

"USP16 mediated DUB of IKKbeta directly, while the USP16 CI mutant lost its ability to regulate IKKbeta ubiquitination, as suggested by in vitro DUB assays (XREF_FIG)."

"The interaction between endogenous c-Myc and USP16 was also demonstrated in PC3 cells (Fig. xref e)."

"The interaction between USP16 and c-Myc protein was assessed by co-immunoprecipitation and protein co-localization assays."

"The interaction between endogenous c-Myc and USP16 was also demonstrated in PC3 cells."

"To further assess the association between USP16 and c-Myc in PCa, we detected the expression of USP16 and c-Myc using tissue microarrays containing 82 human PCa tissues."

"To identify whether USP16 serves as a DUB of c-Myc, HEK293T cells were transfected with plasmids encoding HA-ubiquitin and Flag-c-Myc with wild-type USP16 or its catalytically inactive mutant USP16-C205S and treated with MG132."

"We found that knockdown of USP16 dramatically reduced c-Myc protein abundance but did not affect its mRNA levels, suggesting that the regulation of c-Myc by USP16 occurs at the post-transcriptional level."

"We found that ectopic expression of USP16 enhanced the stability of c-Myc protein, while USP16 knockdown reduced the half-life of c-Myc protein."

"In addition, knockdown of USP16 significantly reduced c-Myc abundance at the post-translational level, while overexpression of wild-type USP16, instead of its catalytic inactive mutant (C205S) [XREF_BIBR], stabilized c-Myc."

"Analysis of c-Myc protein levels by Western blot revealed that knockdown of USP16 significantly decreased the abundance of c-Myc."

"USP16 deubiquitinates c-Myc."

"Besides, the knockdown of USP16 significantly enhanced the polyubiquitination of c-Myc."

"XREF_FIG g, the wild-type USP16, but not USP16-C205S, markedly reduced the ubiquitination of c-Myc."

"In the present study, we found that the targeted disruption of USP16, but not other deubiquitinases of c-Myc, reduced c-Myc protein levels in PCa, indicating that DUBs have different functions in different cancers."

"The histone H2A deubiquitinase USP16 interacts with HERC2 and fine-tunes cellular response to DNA damage."

No evidence text available

No evidence text available

No evidence text available

"This mechanism may explain the evolution of the USP16-HERC2 interaction ( xref , xref , xref online): the USP16 coil-coiled interaction domain at ∼200 a."

No evidence text available

"USP16 interacts with HERC2 and modulates the ubiquitination in DNA repair machinery components ( xref )."

"Here we report that the histone H2A deubiquitinase USP16 interacts with HERC2, fine-tunes the ubiquitin signal during repair, and importantly, is required for terminating the ubiquitination signal after repair."

"USP16 interacts with HERC2 and modulates the ubiquitination in DNA repair machinery components."

"Here we report that the histone H2A deubiquitinase USP16 interacts with HERC2, fine-tunes the ubiquitin signal during repair, and importantly, is required for terminating the ubiquitination signal after repair."

"In response to DNA damage, the HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2)-dependent increase in the level of USP16 negatively regulates ubiquitin foci formation by H2AK119Ub and K15Ub."

"USP16 specifically promotes p105 phosphorylation."

"USP16 specifically promotes p105 phosphorylation."

"In these reconstituted USP16 -/- fibroblasts, USP16 WT, but not USP16 CI, rescued the phosphorylation of p105 and the interaction between IKKbeta and p105 (XREF_FIG)."

"Collectively, these data indicated that the USP16 mediated deubiquitination of IKKbeta may be specifically involved in the phosphorylation and processing of p105."

"USP16 specifically promotes p105 phosphorylation."

"This observation raised a critical question regarding whether USP16 directly regulates IKKbeta activity or p105 phosphorylation."

"USP16 specifically promotes p105 phosphorylation."

"With IKKbeta K238R, USP16 silencing no longer impaired the phosphorylation of p105."

"USP16 deficiency strongly inhibited the activation of p105 by the typical IKK complex under LPS stimulation, as revealed by an in vitro kinase assay (XREF_FIG)."

"We further demonstrated that loss of USP16 specifically causes inactivation of p105 in both BMDMs and MEFs, as indicated by low phosphorylation levels of p105 and low nuclear translocation of p50."

"We further demonstrated that loss of USP16 specifically causes inactivation of p105 in both BMDMs and MEFs , as indicated by low phosphorylation levels of p105 and low nuclear translocation of p50 ."

"Modulation of Ink4a and Arf by Usp16 in Ts65Dn cells."

"USP16 activates Cdkn2a, which acts as a negative regulator of the Wnt signalling pathway."

"USP16 activates Cdkn2a , which acts as a negative regulator of the Wnt signalling pathway ."

"USP16 activates Cdkn2a, which acts as a negative regulator of the Wnt signalling pathway."

"In addition, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts."

"Moreover, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts."

"In Ts65Dn satellite cells, Usp16 expression is increased but we found no evidence of increased p16 Ink4a expression (data not shown)."

"However, lentiviral downregulation of Usp16 with two different hairpins decreased p16 Ink4a and p19 Arf expression (XREF_FIG)."

"The interaction between endogenous c-Myc and USP16 was also demonstrated in PC3 cells (Fig. xref e)."

"The interaction between USP16 and c-Myc protein was assessed by co-immunoprecipitation and protein co-localization assays."

"The interaction between endogenous c-Myc and USP16 was also demonstrated in PC3 cells."

"To further assess the association between USP16 and c-Myc in PCa, we detected the expression of USP16 and c-Myc using tissue microarrays containing 82 human PCa tissues."

"To identify whether USP16 serves as a DUB of c-Myc, HEK293T cells were transfected with plasmids encoding HA-ubiquitin and Flag-c-Myc with wild-type USP16 or its catalytically inactive mutant USP16-C205S and treated with MG132."

"Co-immunoprecipitation and ubiquitination assays confirmed that USP16 served as a novel deubiquitinase of c-Myc and overexpression of c-Myc significantly rescued the effects of USP16 disruption."

"Besides, it remains to explore whether c-Myc signalling could activate USP16 expression, resulting in a positive feedback loop that further promotes tumourigenesis."

"Moreover, c-Myc overexpression restored the proliferation and colony formation abilities of USP16 silenced cells."

"MYSM1 and USP16 activate transcription."

"USP16 activates transcription of HOX genes in a manner consistent with reversing the repressive activity of the Polycomb complex."

"A deubiquitylation enzyme, USP16, negatively regulates uH2A dependent function and rapidly restores transcription after the cessation of DNA damage."

"Similar data were obtained with three separate siRNAs directed against USP16, while expression of a siRNA resistant USP16 allele restored transcription after ATMi (XREF_SUPPLEMENTARY)."

"MYSM1 and USP16 activate transcription."

"USP16 depletion could prevent ATMi mediated restoration of transcription, indicating that this DUB is responsible for de-ubiquitylation of uH2A at DSBs."

"Given that previous studies indicate that H2A ubiquitination regulates Hox gene silencing, it is possible that Usp16 may repress Hox gene expression by modulating the levels of uH2A at the promoter and 5 ' end regulatory region of the Hox gene Finally, there is recent evidence that, in addition to a role in silencing, uH2A may also control transcriptional initiation."

"Knockdown of Usp16 causes a decrease in Hox expression and the rescue from this defect requires the deubiquitinating activity of Usp16."

"Knockdown of Usp16 causes a decrease in Hox expression and the rescue from this defect requires the deubiquitinating activity of Usp16 ."

"The in vivo relevance of Ubp-M mediated Hox gene activation was suggested by the observation that injection of Ubp-M antibodies in Xenopus embryos led to deregulation of HoxD10 expression and defects in posterior development."

"Given that previous studies indicate that H2A ubiquitination regulates Hox gene silencing , it is possible that Usp16 may repress Hox gene expression by modulating the levels of uH2A at the promoter and 5 ' end regulatory region of the Hox gene ( 83 , 153 , 174 , 175 ) Finally , there is recent evidence that , in addition to a role in silencing , uH2A may also control transcriptional initiation ."

"USP16 activates transcription of HOX genes in a manner consistent with reversing the repressive activity of the Polycomb complex."

"Moreover, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts."

"Collectively, USP11 has been clearly linked to essential DDR mechanisms and oncogene-induced senescence, highlighting it as a potentially attractive target for therapeutic agents.In a similar manner to USP3, USP16 has been characterised as an enzyme removing ubiquitin from histone H2A and involved in regulating the RNF8-RNF168 pathway [118] ."

"In hematopoietic stem cells, Usp16 over expression prematurely induces senescence via p16 Ink4a expression 10."

"In addition, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts."

"The deubiquitinating enzyme USP16 suppresses self-renewal and senescence pathways in multiple tissues via deubiquitinating H2AK119 and increasing Ink4a locus transcription [XREF_BIBR], while BMI-1 regulates cell cycle, apoptosis and senescence via inhibiting p16 Ink4a and p19 Arf genes encoded by Ink4a [XREF_BIBR, XREF_BIBR]."

"In this way, USP16 antagonizes the self-renewal and senescence pathways in multiple tissues."

"Cells proliferation were then analysed using a CCK-8 assay, and the results revealed that knockdown of USP16 markedly reduced cell growth in PCa cells."

"Indeed a knockdown of USP16 or an over-expression of its catalytically inactive form slow down cell growth and interfere with mitosis, suggesting that USP16 is the H2A-DUB responsible for histone H2A [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"These results demonstrate that inhibiting USP16 significantly suppressed PCa cell growth in vivo."

"Depletion of USP16 significantly increased the cell growth rate and inhibited cell anoikis in vitro (XREF_FIG and XREF_SUPPLEMENTARY)."

"Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo."

"In addition, USP16 overexpression in normal human fibroblasts and neural progenitors led to reduced cell expansion 159 , which was similar to the strong proliferation defects observed in fibroblasts from individuals with Down syndrome 160 ."

"Discussion Our data show that Bmi1 and Usp16 , important chromatin regulators in stem cells , modulate Wnt signaling in primary mammary epithelial and fibroblast cells ."

"Here we report that Usp16, a negative regulator of Bmi1 and PRC1 function, modulates the Wnt pathway in mammary epithelia, primary human fibroblasts and MEFs, affecting their expansion and self-renewal potential."

"Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation Regulation of the Wnt pathway in stem cells and primary tissues is still poorly understood ."

"Usp16 copy number normalization restores normal Wnt activation in Ts65Dn mice models."

"Usp16 modulates Wnt signaling in primary tissues through Cdkn2a regulation."

"Finally, because of the high prevalence and early appearance of AD in the DS population and the multiple common mechanisms found in both conditions, DS can be considered a useful model to study AD etiopathology and to search for new therapeutic strategies. [188, 191] ↑ in DS and AD Enhancement of lipid, DNA, and RNA oxidation Glutamatergic system [189, 190] ↑ in AD Promotion of OS-induced excitotoxicity Cholinergic system [191] ↓ in DS and AD Aβ-induced enhancement of OS in cholinergic neurons mTOR [192] [193] [194] 196, 198] ↑ in DS and AD OS disruption of mTOR function and mTOR enhancement of oxidative damage Enhanced oxidative stress [191, 200, 201] ↑ in DS and AD Enhancement of ROS-mediated disruption of mitochondrial integrity and function OXPHOS [203] [204] [205] [206] [209] [210] [211] [212] [213] [214] [215] [216] [217] [218] [219] [220] [221] [222] ↓ in DS and AD Enhancement of Aβ production, alterations in cell membranes and synapses, reduction in mitochondrial inner membrane potential, reduction in energy production, and lower mitochondrial function Raptor/mTOR [197, 223, 224] ↑ in DS and AD Alterations in mitochondrial activity and metabolism Insulin signaling [241] [242] [243] ↓ in DS and AD Alterations in energy metabolism, impairment of neuronal activity, plasticity and survival, and facilitation of Aβ aggregation Glucose transport and metabolism [245] [246] [247] [248] [249] [250] ↓ in DS and AD Reduction in energy for synaptic transmission and neurotransmitter biosynthesis, alterations in autophagy PI3-K/Akt/mTOR [65, 67, [253] [254] [255] [256] ↑ in DS and AD Dysregulation of energy balance, induction of insulin resistance, altered autophagy Release of proinflammatory cytokines [269, 270] ↑ in DS and AD Induction of cellular senescence and enhancement by senescence Oxidative stress and mitochondrial dysfunction [15, 262] ↑ in DS and AD Induction of cellular senescence and enhancement by senescence Proteostasis (Aβ and tau) [267, 268] ↑ in DS and AD Induction of cellular senescence and enhancement by senescence, induction of cellular senescence and enhancement by senescence USP16-Wnt [271] [272] [273] ↑ UPS16 in DS/ ↓ Wnt in DS and AD Induction of senescence through DNA damage, downregulation of the Wnt pathway reducing stem cell renewal p38MAPK [281] [282] [283] [284] [285] ↑ in DS and AD Increase in release of cytokines Aβ/APP [287, 290] ↑ in DS and AD Increase in release of cytokines which further aggravates Aβ pathology HPA [292, 293] ↑ in AD Cytokines produce excessive activation of the HPA, which aggravates the energy deficits and enhances OS Inhibition of proliferation and promotion of premature differentiation, prevention the entry into the S phase of the cycle DYRK1A/Notch [312] [313] [314] Inhibition of notch signaling that controls neurogenesis, induction of a shift from neurogenic to glionenic fate of progenitors DYRK1A/NFAT [316] Delay of neurogenesis by the synergic effect with RCAN1 mTOR [317, 318] ↑ in DS and AD Apoptotic death of NPCs BDNF [92, 322] ↓ in DS and AD Impairment of cell proliferation and differentiation Shh [323] [324] [325] ↓ in DS Impairment of proliferation of NPCs •AD, in individuals with or without DS, is a disease with a complex set of neuropathological signs. •Numerous signalling pathways are implicated in the onset and aggravation of this neuropathology. •The same signalling pathway often plays a role in the appearance or progression of different signs of AD. •In many cases, synergic effects and feedback loops exist between these pathways. •Because of the complex etiopathology of AD and the interrelation between the factors responsible for the symptoms of the disease, therapeutic approaches should combine different targets. • AD, in individuals with or without DS, is a disease with a complex set of neuropathological signs."

"Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and postnatal neural progenitors, whereas downregulation of USP16 partially rescues the proliferation defects of Down 's syndrome fibroblasts."

"Concordantly, we found that ectopic expression of USP16 mostly restored the proliferation rate of USP16 knockdown cells."

"Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and post-natal neural progenitors while downregulation of USP16 partially rescues the proliferation defects of DS fibroblasts."

"USP16 is upregulated in Down 's syndrome (DS) cells due to extrachromosomal triplication in trisomy 21, downregulation of USP16 partially restores the impaired proliferation in DS somatic stem cells."

"These results were further confirmed by the fact that depleting USP16 promoted cell proliferation in Hs683 and SW1783 cells ( fig ."

"In contrast to observations in ESCs and HSCs , USP16 deficiency did not increase ubH2A levels ( fig ."

"When ESCs are differentiated, Usp16 is required to reverse ubH2A mediated gene repression and enables gene activation and subsequent ESC differentiation."

"In contrast to observations in ESCs and HSCs, USP16 deficiency did not increase ubH2A levels."

"Supporting our biochemical assays, Usp16 knockout caused a significant increase of ubH2A levels without any apparent effects on H2A levels (XREF_FIG)."

"Depletion of USP16 was shown to significantly suppress the growth of PCa cells both in vitro and in vivo."

"Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo."

"USP16 knockdown suppresses growth of PCa tumour xenografts."

"These results demonstrate that inhibiting USP16 significantly suppressed PCa cell growth in vivo."

"This result indicates a clear pivotal effect of myeloid USP16 mediated canonical NF-kappaB in experimental colitis model establishment and CRC development."

"In addition, transfection of USP16 WT, but not USP16 CI, increased TNF-alpha-induced NF-kappaB activity in HEK293T cells, as demonstrated by NF-kappaB luciferase reporter assays (XREF_FIG and fig."

"Notably, USP16 deficiency greatly impaired the activation of NF-kappaB induced by TNF-alpha (XREF_FIG)."

"Three bona fide NFkappaB binding sites were found in USP16 promoter."

No evidence text available

No evidence text available

"Both USP3 and USP16 are also associated with H2A deubiquitination following DNA damage processing [ xref , xref ]."

No evidence text available

No evidence text available

No evidence text available

"Whether USP16 targets the products of RNF8 and RNF168- and/or BMI1 and RING1B dependent ubiquitylation remains to be established."

"Furthermore inhibition of USP16 activity in vivo in Xenopus embryos similarly reduced HoxD10 gene expression, and resulted in abnormalities in the anterior-posterior patterning of the embryos (Joo et [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Knockdown of USP16 or an over-expression of its catalytically inactive form in cell lines increased H2AK119Ub levels both globally and at the HoxD10 locus, and suppressed HoxD10 gene expression (Cai e[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"ChIP studies on HOXD10 binding of USP16 and the BMI1 subunit of PRC1 found both proteins are localized to the HOXD10 promoter, yet H2A was not ubiquitinated unless USP16 was depleted."

"Thus, the increased Usp16 expression in TS65Dn satellite cells could disrupt DNA repair, induce DNA damage, and impair satellite cell expansion."

"Overexpression of USP16 may induce excessive DNA damage accumulation, leading to acquisition of prematurely senescent phenotypes in different DS cell types [272, 274]."

"Since elevated Usp16 expression contributes to somatic stem cell dysfunction in Down syndrome 10 and Usp16 represses DNA damage responses XREF_BIBR, XREF_BIBR, we asked if Ts65Dn satellite cells accumulate more DNA damage that wild type satellite cells."

"In addition, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts."

"Moreover, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts."

"Usp16 regulation of the Wnt pathway in mouse and human tissues is at least in part mediated by activation of Cdkn2a, a regulator of senescence."

"Furthermore, LPS and TNFalpha, strong activators of the NFkappaB pathway, upregulated the USP16 transcription."

"Furthermore, we observed significant reductions in nuclear p50 levels and small decreases in nuclear translocated c-Rel and p65 levels in LPS stimulated USP16 deficient BMDMs (XREF_FIG)."

No evidence text available

No evidence text available

No evidence text available

"Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression."

"IHC staining analysis of the xenograft tissues revealed that inhibiting USP16 reduced Ki67 expression, indicating USP16 knockdown impaired the proliferation of PCa cells."

"IHC staining analysis of the xenograft tissues revealed that inhibiting USP16 reduced Ki67 expression , indicating USP16 knockdown impaired the proliferation of PCa cells ( Fig. 3d-f ) ."