IndraLab

Statements

VCPIP1 is modified

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VCPIP1 is phosphorylated.

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VCPIP1 is phosphorylated. 10 / 78

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"We next investigated the effect of several protein kinase inhibitors on the mitotic phosphorylation of VCIP135 ( Fig. 1 B, lanes 2–7)."

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"Staurosporine (broad serine/threonine kinase inhibitor) and olomoucine (Cdc2 inhibitor) inhibited VCIP135 phosphorylation (lanes 2 and 3)."

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"On the other hand, neither PD98059 (MEK inhibitor), SB203580 (p38 MAP kinase inhibitor), KT5720 (protein kinase A inhibitor) nor calphostin C (protein kinase C inhibitor) had any effect on VCIP135 pho[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"It is known that the phosphorylation of VCIP135 during mitosis disrupts its association with p97 ( xref , xref )."

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"Mitotic phosphorylation of VCIP135 blocks p97ATPase-mediated Golgi membrane fusion."

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"This is also found with DUBs, as exemplified by the regulated expression and phosphorylation of A20, and the phosphorylation of VCIP135 ( xref ; xref ; xref )."

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"VCPIP1 is phosphorylated by ATM/ATR upon DPC induction."

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"As shown in xref , following FA and CPT treatment, VCPIP1 was phosphorylated at its SQ/TQ motifs, which are consensus ATM/ATR phosphorylation sites."

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"Nuclear VCPIP1 was phosphorylated at the SQ/TQ motif in wild-type but not ATM-deficient cells ( xref )."

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"These results suggest that VCPIP1 is phosphorylated by ATM/ATR following DPC induction."

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VCPIP1 is phosphorylated on S131. 10 / 41

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"We next determined the kinase responsible for VCIP135 S130 phosphorylation in mitosis."

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"Mitotic phosphorylation of VCIP135 at S130 inhibits its deubiquitinase activity."

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"Phosphorylation of VCIP135 on S130 attenuates p97/p47-mediated Golgi membrane fusion."

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"VCIP135 S130 is phosphorylated in prometaphase and dephosphorylated in telophase."

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"Because S130 matches the minimal S/T-P consensus motif for both Cdk1 (Nigg, 1993) and ERK1/2 (Davis, 1993; Songyang ), we applied inhibitors to these protein kinases to mitotic cells and investigated the effects on S130 phosphorylation of VCIP135."

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"Taken together, these results demonstrate that the pSer130 antibody specifically recognizes phosphorylated S130 of VCIP135."

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"To determine the phosphorylation state of VCIP135 on S130 during cell cycle progression, we developed an antibody that specifically recognizes phosphorylated S130 on VCIP135."

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"To determine the phosphorylation state of VCIP135 on S130 during cell cycle progression, we developed an antibody that specifically recognizes phosphorylated S130 on VCIP135. We used the phosphopeptide KLL[pS]PILARY as the antigen, because this sequence is well conserved between species (Figure 2D). The generated antibody, here referred to as “the VCIP135 pSer130 antibody,” specifically recognizes VCIP135 immunoprecipitated from mitotic but not from interphase cells (Figure 3A, top panel), consistent with the mobility shift of VCIP135 in mitosis (Figure 3A, bottom panel). We further confirmed its specificity using VCIP135 phosphomutants immunoprecipitated from interphase (Figure 3B) or mitotic cells (Figure 3C). The VCIP135 pSer130 antibody recognized the S130E and 13E mutants in both interphase and mitotic cells, but had no immunoreactivity to the S130A and 13A mutants, regardless of the cell cycle stage (Figure 3, B and C). WT VCIP135 and the C218S, 12A, and 12E mutants were phosphorylated at S130 and were recognized by the pSer130 antibody only in mitotic cells."

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"It was also reported that VCIP135 is mitotically phosphorylated on Ser-130, which weakens its binding to p97 ( xref )."

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"Taken together, our results demonstrate that phosphorylation of VCIP135 on S130 in early mitosis inactivates its DUB activity for mitotic Golgi disassembly; dephosphorylation in telophase reactivates VCIP135 to promote p97/p47-mediated postmitotic Golgi membrane fusion."

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VCPIP1 is phosphorylated on T761. 6 / 6

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"All these results indicate that phosphorylation of Threonine-760 and Serine-767 in VCIP135 inhibits its binding to p97."

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"In summary, our biochemical data show that phosphorylation of Threonine-760 and Serine-767 in VCIP135 inhibits its binding to p97, but does not affect its binding to WAC nor its deubiquitinating activ[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"We established that VCIP135 is mitotically phosphorylated at Threonine-760 and Serine-767 and that the phosphorylated VCIP135 cannot bind to p97."

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"Taken together, these results demonstrate that the phosphorylation of Threonine-760 and Serine-767 in VCIP135 inhibits both p97-mediated Golgi reassembly pathways, indicating that it is important for [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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VCPIP1 is phosphorylated on S768. 5 / 5

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"All these results indicate that phosphorylation of Threonine-760 and Serine-767 in VCIP135 inhibits its binding to p97."

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"Our results indicate that the phosphorylation of VCIP135 on Threonine-760 and Serine-767 inhibits p97-mediated Golgi membrane fusion at mitosis."

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"We established that VCIP135 is mitotically phosphorylated at Threonine-760 and Serine-767 and that the phosphorylated VCIP135 cannot bind to p97."

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VCPIP1 is phosphorylated on S1198. 3 / 3

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VCPIP1 is phosphorylated on S994. 3 / 3

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VCPIP1 is phosphorylated on S747. 3 / 3

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VCPIP1 is phosphorylated on S997. 2 / 2

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VCPIP1 is phosphorylated on S1132. 2 / 2

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VCPIP1 is phosphorylated on Y767. 2 / 2

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VCPIP1 is phosphorylated on S757. 2 / 2

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VCPIP1 is phosphorylated on S998. 2 / 2

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VCPIP1 is dephosphorylated. 5 / 5

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"Conversely, at the end of mitosis, VCIP135 is dephosphorylated (on Ser130), and this is associated with recovery of its deubiquitinase activity and with post-mitotic Golgi reassembly (Zhang and Wang, xref )."

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"Dephosphorylation of VCIP135 at S130 in telophase activates its deubiquitinase activity for Golgi reassembly."

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"During late mitosis, VCIP135 becomes dephosphorylated and associates with the p97–p47–Syn5 complex."

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"Dephosphorylation of S130 on VCIP135 upon staurosporine or roscovitine but not U0126 treatment also significantly increased the DUB activity of endogenous VCIP135 ( xref ), consistent with the hypothesis that phosphorylation at S130 inactivates VCIP135."

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VCPIP1 binds VCP. 10 / 61

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"Overall, our study not only reveals the unexpected interaction and organization of human P97/VCP‐VCPIP1 complex, but also provides crucial insights into the mechanism of VCPIP1‐P97/VCP mediated Golgi biogenesis.2 Results."

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"To validate the direct interaction between VCPIP1 and P97/VCP in vitro, we first purified the full‐length proteins and analyzed their interactions by size exclusion chromatography."

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"The obtained result showed that the VCPIP1 could directly bind to P97/VCP by migrating together with P97/VCP on the size exclusion column (Figure 1B)."

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"The results reveal that, in the absence of substrates, the binding of VCPIP1 to P97/VCP led to a marginal increase in its activity (Figure 1E).2.2 Cryo-EM Structure of VCPIP1-P97/VCP Complex."

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"Albeit with the relatively lower and heterogeneous resolution of VCPIP1, the regions of VCPIP1 that directly contact P97/VCP could be readily and confidently modeled.Expectedly, the P97/VCP in the P97/VCP‐VCPIP1 complex was folded into the canonical homo‐hexamer as previously studied (Figure 2A,C)."

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"Unexpectedly, three VCPIP1 molecules directly bind to the C‐terminal D2 ATPase domain of the P97/VCP, resulting in the formation of P97/VCP‐VCPIP1 complex with a stoichiometry of 2:1 (Figure 2B)."

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"Since only one 3D reconstruction was obtained and could be refined to high resolution from our cryo‐EM studies, we favored it as the stable and dominant conformation adopted by the full‐length P97/VCP‐VCPIP1 complex (Figure S1C, Supporting Information)."

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"However, the ATPase assay revealed that VCPIP1 binding to P97/VCP only slightly increases its ATPase activity (Figure 1E).2."

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"Golgi WAC interacts with the deubiquitinase VCIP135, which binds VCP and p97."

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VCPIP1 activates VCP. 5 / 5

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"VCPIP1 S130 was phosphorylated by Cdk1 in early mitosis and then inactivated to block the P97/VCP‐P47 mediated Golgi membrane fusion."

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"Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. |We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97."

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"30 , 31 Our structure indicates that the binding of VCPIP1 to the D2 domain of P97/VCP would induce a conformational change, promoting P97/VCP into the NTDs “UP” state."

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"22 Consistently, our studies have demonstrated that VCPIP1 biochemically promotes P97/VCP‐p47 binding to SNARE substrates, the addition and binding of WAC protein to VCPIP1 might further stimulate their binding for membrane fusion.Recently, VCPIP1 has been reported to associate with both the N‐ and C‐terminal regions of P97/VCP via its C‐ and N‐terminal regions, respectively."

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"In particular, as p47, p37, Ufd1, and VCIP135 share the same p97-binding motif (SHP motif), it is reasonable that VCIP135 may induce the dissociation of complexes of p97 with p47, p37, and Ufd1."

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VCPIP1 inhibits VCP.

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VCPIP1 inhibits VCP. 1 / 1

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"VCPIP1 S130 was phosphorylated by Cdk1 in early mitosis and then inactivated to block the P97/VCP‐P47 mediated Golgi membrane fusion."

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VCP affects VCPIP1

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VCP binds VCPIP1.

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VCPIP1 binds VCP. 10 / 61

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"To validate the direct interaction between VCPIP1 and P97/VCP in vitro, we first purified the full‐length proteins and analyzed their interactions by size exclusion chromatography."

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"The obtained result showed that the VCPIP1 could directly bind to P97/VCP by migrating together with P97/VCP on the size exclusion column (Figure 1B)."

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"The results reveal that, in the absence of substrates, the binding of VCPIP1 to P97/VCP led to a marginal increase in its activity (Figure 1E).2.2 Cryo-EM Structure of VCPIP1-P97/VCP Complex."

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"However, the ATPase assay revealed that VCPIP1 binding to P97/VCP only slightly increases its ATPase activity (Figure 1E).2."

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"Golgi WAC interacts with the deubiquitinase VCIP135, which binds VCP and p97."

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Mutated VCPIP1 binds VCP. 1 / 1

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"VCIP135 mutants with only one of the two p97 binding interactions still formed a complex with p97 (Fig. 5A)."

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VCP activates VCPIP1. 3 / 3

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"We observe competition between VCPIP1 and other cofactors for VCP binding and show that VCP stimulates VCPIP1's DUB activity."

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"Skillfully reversing ubiquitination, the deubiquitinase VCIP135 mediated by VCP/NSFL1C takes charge of orchestrating a seamless remodeling of the Golgi membrane (36, 39)."

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"We find that VCP stimulates VCPIP1's DUB activity and use mutagenesis and single-molecule mass photometry assays to test the structural model."

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CDK1 affects VCPIP1

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CDK1 phosphorylates VCPIP1.

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CDK1 phosphorylates VCPIP1. 10 / 19

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"All these results indicate that phosphorylation of Threonine 760 and Serine 767 in VCIP135 inhibits its binding to p97.We next tested the binding of phosphorylated VCIP135 to WAC, as presented in Fig.[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"VCIP135 phosphorylated by Cdc2 generated almost the same amount of mono ubiquitin after the reaction as non phosphorylated VCIP135."

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"To confirm this, we investigated whether the purified Cdc2 complex phosphorylated VCIP135 in the absence of mitotic cytosol."

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"As shown in Fig. 1 C, Cdc2 indeed phosphorylated VCIP135 (right lane)."

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"We show that, in early mitosis, phosphorylation of VCIP135 by Cdk1 at a single residue, S130, is sufficient to inactivate the enzyme and inhibit p97/p47-mediated Golgi membrane fusion."

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"We next tested the binding of phosphorylated VCIP135 to WAC, as presented in Fig. 3 A. Cdc2-phosphorylated VCIP135 still bound to GST-WAC (upper panel, lane 2), suggesting that the phosphorylation of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"VCIP135 phosphorylated by Cdc2 generated almost the same amount of mono ubiquitin after the reaction as non-phosphorylated VCIP135 ( Fig. 3 C, top panel, lane 2)."

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"Phosphorylation of VCIP135 on S130 by the mitotic kinase Cdk1 in early mitosis abolishes its deubiquitinase activity and attenuates p97/p47-mediated Golgi membrane fusion."

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"During mitosis, Cdk1 phosphorylates p47, p37 and VCIP135, and blocks p97-controlled membrane-fusion processes so that the Golgi membranes remain disassembled (Uchiyama et al., xref ; Kaneko et al., xref ; Totsukawa et al., xref )."

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"Cdk1 phosphorylates VCIP135 at S130."

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CDK1 phosphorylates VCPIP1 on S131. 10 / 15

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"Cdk1 phosphorylates VCIP135 at S130."

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"Therefore Cdk1 directly phosphorylates VCIP135 on S130 in mitosis."

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"These results suggest that VCIP135 is phosphorylated on S130 by the mitotic kinase Cdk1."

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"To determine whether Cdk1 directly phosphorylates VCIP135 on S130, we performed an in vitro phosphorylation assay with streptavidin binding peptide (SBP)-tagged VCIP135 recombinant proteins."

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"Therefore Cdk1 directly phosphorylates VCIP135 on S130 in mitosis."

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"We show that, in early mitosis, phosphorylation of VCIP135 by Cdk1 at a single residue, S130, is sufficient to inactivate the enzyme and inhibit p97/p47-mediated Golgi membrane fusion."

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"Note that Cdk1 directly phosphorylates VCIP135 on S130."

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"Cdk1 phosphorylates VCIP135 at S130."

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No evidence text available

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"Phosphorylation of VCIP135 on S130 by the mitotic kinase Cdk1 in early mitosis abolishes its deubiquitinase activity and attenuates p97/p47-mediated Golgi membrane fusion."

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CDK1 phosphorylates VCPIP1 on S768. 8 / 9

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"We show that VCIP135 is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis."

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"We show that VCIP135 is phosphorylated on Threonine 760 and Serine 767 by Cdc2 at mitosis."

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biopax:phosphositeplus

No evidence text available

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"We previously showed that VCIP135 is phosphorylated on Thr-760 and Ser-767 by Cdc2 during mitosis and that the phosphorylation of VCIP135 decreases its binding affinity for p97 and inhibits p97-mediated Golgi membrane fusion during mitosis ( xref )."

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"Taken together, we conclude that VCIP135 is mitotically phosphorylated on Threonine-760 and Serine-767 by Cdc2."

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"We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97."

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CDK1 phosphorylates VCPIP1 on T761. 7 / 8

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"We show that VCIP135 is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis."

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"Taken together, we conclude that VCIP135 is mitotically phosphorylated on Threonine-760 and Serine-767 by Cdc2."

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"We show that VCIP135 is phosphorylated on Threonine 760 and Serine 767 by Cdc2 at mitosis."

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CDK1 inhibits VCPIP1.

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CDK1 inhibits VCPIP1. 2 / 2

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P97 affects VCPIP1

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VCPIP1 binds p97. 10 / 38

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"The next question was, which region of p97 interacts with the two distinct binding sites in VCIP135?"

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"These results strongly suggest that VCIP135 can associate with p97 via two distinct interactions."

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"We next aimed to generate mutants of these two p97-binding regions in VCIP135 that do not bind to p97."

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"Full-length VCIP135 associates with p97 through their two distinct interactions."

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"As shown in xref B , the complex of VCIP135(F1024L/L1031P) and p97 was able to associate with another VCIP135 molecule (lane 3)."

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"These results indicate that p97 can associate with two VCIP135 molecules using the two binding interactions."

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"In other words, these results strongly support the fact that each of the two distinct binding interactions between VCIP135 and p97 is sufficient for VCIP135-p97 complex formation."

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"We also investigated the nucleotide dependency of the two interactions between VCIP135 and p97 using these full-length VCIP135 mutants."

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"Although VCIP135 also binds to p97 [13] , it remains unclear whether complex formation between VCIP135 and p97 is really necessary for p97-mediated membrane fusion."

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"We also showed that the binding of VCIP135 to p97 does not change its deubiquitinating activity ( xref )."

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VCPIP1 binds SNTG2, p47, and p97. 2 / 2

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"During late mitosis, VCIP135 becomes dephosphorylated and associates with the p97–p47–Syn5 complex."

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"At this time VCIP135 is inactivated by mitotic phosphorylation ( xref ; xref ) and thus monoubiquitinated Syn5, p97, p47, and VCIP135 form a transient quaternary complex ( xref )."

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VCPIP1 binds STX5, p97, and p47. 2 / 2

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"This simple binding experiment showed that VCIP135 can form a quaternary complex with syntaxin5, p97, and p47 (Fig. S2 available at)."

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VCPIP1 binds X.

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X binds VCPIP1. 10 / 22

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"The GST pulldown assay demonstrated that VCPIP1 bound to HBx directly ( xref ) in vitro ."

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"The HBx C-terminal sequence, spanning aa 121 to 154, predominated in the HBx-VCPIP1 binding, as seen in the colony abolishment in the yeast two-hybrid assay with pGBKT7-HBxΔ121–154, which lacked the sequences ( xref )."

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"These results demonstrate that the interaction between HBx and VCPIP1 may increase HBx stability."

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"Co-immunoprecipitation (Co-IP) assay using cell lysates demonstrated the association of HBx with both endogenously and exogenously expressed VCPIP1 ( xref Fig. S1), while co-IP using in vitro -translated proteins confirmed a direct binding between HBx and VCPIP1 ( xref )."

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"We, therefore, tested whether these domains were involved in VCPIP1-HBx binding."

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"The mutual interactions between VCPIP1 and HBx ( xref ), HBx and PSMC3 ( xref ), and PSMC3 and VCPIP1 ( xref ) were identified."

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"Combined with the earlier results demonstrating that HBx aa 121 to 154 and VCPIP1 aa 863 to 1221 were required for VCPIP1-HBx interaction ( xref and xref ), we narrowed down the sequence for interacting with HBx to VCPIP1 C-terminal aa 863 to 982 ( xref )."

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"First, we reported that VCPIP1 bound directly to HBx through its C-terminal aa 863 to 1221, and the interacting sequences were sufficient for HBx stability even in the absence of its N-terminal enzymatic activity."

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"Furthermore, VCPIP1-HBx interaction appears to facilitate HBx protein to exert its pleiotropic effects including canonical transactivational activity and cell proliferation inhibition, suggesting its potential role in the pathogenesis of HBV-related hepatocellular carcinoma."

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"Functionally, HBx specifically binding to VCPIP1 significantly enhanced the transcriptional transactivation of HBx by activating NF-kappaB, AP-1, and SP-1 and inhibited hepatoma cell clonogenicity in Huh7 and HepG2 cells."

35695579

VCPIP1 activates X.

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VCPIP1 activates X. 9 / 9

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"Although VCPIP1 overexpression led to significantly increased HBx in the Huh7 and HepG2 cells, it did not redice the amounts of HBx ubiquitination (Fig. 4C)."

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"RNA interference (RNAi) targeting endogenous PSMC3 was used to validate that PSMC3 was required for VCPIP1-mediated HBx stability but was not a contributing factor."

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"Collectively, the results indicate that VCPIP1-recruited PSMC3 associating with HBx functionally prevents the HBx degradation by the 20S proteasome."

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"As expected, ectopic VCPIP1 expression led to significantly increased HBx in a dose-dependent manner in both Huh7 and HepG2 cells (Fig. 2B)."

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"Then, the similar effects of VCPIP1 and its C-terminal truncation increasing the HBx expression were validated in HepG2.2.15 cells (Fig. 2G), but HBx was reduced by silencing endogenous VCPIP1 (Fig. 2H)."

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"VCPIP1 increases HBx stability.."

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"VCPIP1 inhibits HBx degradation through the proteasome pathway in a ubiquitin-independent manner.."

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"PSMC3 , encoding the 26S proteasome regulatory subunit , directly stabilized HBx through physical binding instead of a common approach in protein degradation , serving as the key downstream effector of VCPIP1 on HBx ."

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"Finally, the VCPIP1-induced HBx stability greatly promoted its canonical transcriptional activities and contributed to the inhibition of colony formation of Huh7 and HepG2 cells."

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VCPIP1 activates X. 1 / 1

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"Collectively, these results showed that VCPIP1 positively regulates HBx protein stability by slowing down its degradation through the proteasomal pathway."

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VCPIP1 increases the amount of X.

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VCPIP1 increases the amount of X. 5 / 5

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"VCPIP1 and its C-terminal amino acids 863 to 1221 upregulated the HBx protein expression, with or without HBV infection."

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"Regarding the DUB nature of VCPIP1 in the OTU subfamily, we presumed that VCPIP1 would increase the HBx protein expression."

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"To verify the VCPIP1-induced increase in the HBx protein levels, we used cycloheximide (CHX) to block protein synthesis to determine whether VCPIP1 altered HBx stability."

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"Conversely, knockdown of endogenous VCPIP1 expression in these models resulted in inhibition of HBV transcription and replication, along with moderately decreased production of secreted antigens, and reduced HBx protein levels (Fig. 2B)."

39494904

➶

reach

"Clearly, upregulation of HBx protein level by VCPIP1-mediated stabilizing is also effective in these models of HBV replication and correlated with upregulated HBV gene expression and genome replication."

39494904

VCPIP1 increases the amount of X. 4 / 4

| 4

➶

reach

"Both the full-length VCPIP1 and its C-terminal aa 863 to 1221 upregulated the HBx expression induced by plasmid containing replication-competent full-length HBV (Fig. 2E and F)."

35695579

➶

reach

"Functionally, ectopic VCPIP1 expression increased HBx expression in a dose-dependent manner and in the context of HBV infection."

35695579

➶

reach

"To determine whether the increased HBx expression by VCPIP1 was due to the decreased ubiquitination, we performed an in vivo ubiquitination assay by detecting the ubiquitination of HBx proteins using the Flag antibody-conjugated agarose beads to precipitate the HBx."

35695579

➶

reach

"More importantly, it was clearly shown that siPSMC3 treatment greatly impaired the HBx expression increased by VCPIP1 overexpression compared to the siRNA control (Fig. 6F)."

35695579

VCPIP1 affects SPRTN

5 1 | 1 30 4

VCPIP1 deubiquitinates SPRTN.

1 | 20

VCPIP1 deubiquitinates SPRTN. 10 / 21

1 | 20

➶

reach

"Upon DPC induction, ATM and ATR kinase activates VCPIP1 and VCIP135 deubiquitinase, which in turn deubiquitinates SPRTN, regulating its chromatin localization."

33567341

➶

reach

"Deubiquitination of SPRTN by VCPIP1 is important for DPC repair."

32649882

➶

reach

"These results suggest that VCPIP1 deubiquitinates SPRTN both in vitro and in cells."

32649882

➶

reach

"These observations show that depletion of USP11 and VCPIP1 inhibits SPRTN deubiquitination, but in contrast to previous reports, monoubiquitination does not restrict SPRTN access to chromatin."

33567341

➶

reach

"Taken together, our data indicate that VCPIP1 regulates SPRTN via its Ub protease activity and deubiquitination of SPRTN by VCPIP1 is important for its chromatin retention in response to DPC lesions."

32649882

➶

reach

"We found that knockdown of VCPIP1 decreased acetylation of SPRTN upon DPC induction (Figure 4I), suggesting that SPRTN acetylation requires SPRTN deubiquitination."

32649882

➶

reach

"VCPIP1, in turn, deubiquitinates SPRTN and promotes its chromatin relocalization."

32649882

➶

ubibrowser

"Previously, VCPIP1 and USP7 deubiquitinases have been shown to regulate SPRTN"

33567341

➶

reach

"The DUB VCPIP1/VCIP135 also deubiquitinates SPRTN after being phosphorylated and activated by ATM/ATR."

37728310

➶

reach

"VCIP135 was reported to function as a deubiquitinating enzyme without the assistance of p97; that is, in the activation of SPRTN, a specialized DNA-dependent metalloprotease, VCIP135 deubiquitinated SPRTN in the absence of p97 (12)."

38072049

VCPIP1 binds SPRTN.

5 | 5 4

SPRTN binds VCPIP1. 10 / 14

5 | 5 4

➶

sparser

"Moreover, after treating cells with three known DPC-inducing agents, FA, camptothecin (CPT) and cisplatin ( xref ), the interaction between VCPIP1 and SPRTN increased ( xref and xref – xref )."

32649882

➶

reach

"Consistent with the interaction shown by co-immunoprecipitation, direct association between VCPIP1 and SPRTN in cells was confirmed by proximity ligation assay (PLA) and PLA foci signals were mostly in the nucleus and significantly increased after FA treatment (Figures 1D–1E)."

32649882

➶

sparser

"Our data strongly suggest that VCPIP1-SPRTN signaling axis is the key regulation in DPC repair."

32649882

➶

sparser

"As VCPIP1-SPRTN signaling protects cells from DPC induction, it seems likely that inhibition of VCPIP1-SPRTN could be employed to sensitize cells to different kinds of DPC-inducing agents."

32649882

➶

reach

"Knockdown of VCP did not change the SPRTN/VCPIP1 interaction (Figure S2J)."

32649882

➶

biogrid

No evidence text available

32649882

➶

biogrid

No evidence text available

32649882

➶

biogrid

No evidence text available

32649882

➶

biogrid

No evidence text available

32649882

➶

reach

"VCPIP1 and USP11 interact weakly with SPRTN in co-immunoprecipitating experiments, but show no (VCPIP1) or only weak (USP11) preference for SPRTN-Ub (XREF_SUPPLEMENTARY)."

33348378

VCPIP1 activates SPRTN.

| 1 3

VCPIP1 activates SPRTN. 4 / 4

| 1 3

➶

reach

"Huang et al. reported that knockdown of VCPIP1 prevented SPRTN chromatin localization upon formaldehyde treatment, in agreement with previous reports that monoubiquitinated SPRTN is excluded from the chromatin (Stingele et al., 2016; Huang et al., 2020)."

35782873

➶

eidos

"Knockdown of VCPIP1 greatly reduced the interaction between SPRTN and PCAF / GCN5 in the presence of DPCs ( Figure S4H ) , suggesting that VCPIP1 is required to bring acetyltransferases to SPRTN in a DPC-dependent manner ."

32649882

➶

reach

"Thus, the identification of VCPIP1 as a dual promoter of SPRTN deubiquitination and acetylation may mean that knockdown of VCPIP1 is dysregulating SPRTN at multiple steps, and that SPRTN acetylation may be the signal for its chromatin retention upon DPC induction rather than deubiquitination (Table 1)."

35782873

➶

reach

"However, VCIP135 was reported to function without the assistance of p97 in the activation of SPRTN, a specialized DNA-dependent metalloprotease (12)."

38072049

VCPIP1 inhibits SPRTN.

| 1

VCPIP1 inhibits SPRTN. 1 / 1

| 1

➶

reach

35782873

VCPIP1 acetylates SPRTN.

| 1

VCPIP1 leads to the acetylation of SPRTN. 1 / 1

| 1

➶

reach

"We found that knockdown of VCPIP1 decreased acetylation of SPRTN upon DPC induction (Figure 4I), suggesting that SPRTN acetylation requires SPRTN deubiquitination."

32649882

VCPIP1 affects STX5

2 2 | 11 15

VCPIP1 binds STX5.

2 2 | 8 15

STX5 binds VCPIP1. 10 / 30

2 1 | 7 12

➶

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"In the presence of ATP, the addition of VCIP135 prevented p97 and p47 from binding to syntaxin5 and VCIP135 itself only bound poorly to syntaxin5 ( xref D, left three lanes)."

12473691

➶

reach

"The binding of VCIP135 to syntaxin5 independently of p47 (XREF_FIG C) allows VCIP135 to be closely associated with the p97 and p47 complex, whereas in cytosol such an association is less likely."

12473691

➶

sparser

"However, in the presence of AMP–PNP or ADP, p97 and p47 bound to syntaxin5 even when VCIP135 was added, and VCIP135 also bound to syntaxin5 ( xref D, right six lanes)."

12473691

➶

sparser

"These data suggest that both VCIP135 and the p97/p47 complex bind to syntaxin5, resulting in the formation of a transient quaternary complex that could be dissociated through p97 ATP hydrolysis."

12473691

➶

sparser

"Although VCIP135 can bind to p97 in cytosol ( xref A), VCIP135 bound to syntaxin5 does not form a complex with p97 ( xref C, lane 4)."

12473691

➶

sparser

"The addition of p97 decreased the amount of VCIP135 bound to syntaxin5 ( xref F)."

12473691

➶

sparser

"We have shown that VCIP135 binds to syntaxin5 and disassembles the p97/p47/syntaxin5 complex through p97 ATP hydrolysis."

12473691

➶

sparser

"VCIP135 bound to syntaxin5 is thought to associate with a syntaxin5-bound p97/p47 complex with syntaxin5 acting as a scaffold for the p97/p47 dissociation reaction."

12473691

➶

sparser

"The binding of VCIP135 to syntaxin5 independently of p47 ( xref C) allows VCIP135 to be closely associated with the p97/p47 complex, whereas in cytosol such an association is less likely."

12473691

➶

sparser

"VCIP135 forms a quaternary complex with syntaxin 5 and the p97/p47 complex via a ubiquitin fold domain and its enzymatic activity is required for post-mitotic Golgi membrane fusion xref ."

23453991

VCPIP1 binds STX5, p97, and p47. 2 / 2

| 2

➶

sparser

"This simple binding experiment showed that VCIP135 can form a quaternary complex with syntaxin5, p97, and p47 (Fig. S2 available at)."

12473691

➶

sparser

"VCIP135 binds to the p97–p47–syntaxin-5 complex and can dissociate p97 and p47 from syntaxin-5 ( xref )."

15037600

VCPIP1 binds p97 and STX5. 1 / 1

| 1

➶

sparser

"VCIP135 did not bind to syntaxin5 with p97 ( xref C, lane 4), a finding which was investigated further ( xref F)."

12473691

GEMIN4 binds VCPIP1 and STX5. 1 / 1

| 1

➶

reach

"Since the p97, VCIP135, and syntaxin5 complex is very unstable (XREF_FIG C), a tighter VCIP135 and p97 complex then dissociates from syntaxin5 (XREF_FIG F)."

12473691

VCP binds STX5, NSFL1C, and VCPIP1. 1 / 1

1 |

➶

hprd

No evidence text available

12473691

VCPIP1 activates STX5.

| 2

VCPIP1 activates STX5. 2 / 2

| 2

➶

reach

31435807

➶

reach

"As shown in XREF_FIG G, VCIP135 partially prevented alpha-SNAP binding to GST-syn5DeltaTM, suggesting that VCIP135 directs syntaxin5 to p97 and p47 but not to alpha-SNAP and NSF."

12473691

VCPIP1 deubiquitinates STX5.

| 1

VCPIP1 deubiquitinates STX5. 1 / 1

| 1

➶

reach

"Syntaxin 5 is monoubiquitinated by HACE1 in early mitosis and deubiquitinated by the de-ubiquitinase VCIP135 in late mitosis."

31435807

VCPIP1 affects GEMIN4

| 32

VCPIP1 binds GEMIN4.

| 25

VCPIP1 binds GEMIN4. 10 / 16

| 16

➶

reach

"After incubation, the p97 bound to p47 was coimmunoprecipitated by anti-p47 antibodies in order to separate it from the p97 bound to VCIP135."

12473691

➶

reach

"Although VCIP135 also binds to p97 [13], it remains unclear whether complex formation between VCIP135 and p97 is really necessary for p97 mediated membrane fusion."

23500464

➶

reach

"We have shown that VCIP135 binds to syntaxin5 and disassembles the p97, p47, and syntaxin5 complex through p97 ATP hydrolysis."

12473691

➶

reach

"VCIP135 binds to the p97, p47, and syntaxin-5 complex and can dissociate p97 and p47 from syntaxin-5."

15037600

➶

reach

"During late mitosis, VCIP135 becomes dephosphorylated and associates with the p97, p47, and Syn5 complex."

28819009

➶

reach

"Golgi WAC interacts with the deubiquitinase VCIP135, which binds VCP and p97."

26687599

➶

reach

"VCPIP1 interacts with p97, a highly abundant protein implicated in a vast range of cellular activities including the endoplasmic reticulum associated degradation (ERAD) pathway and HIF1alpha stability XREF_BIBR."

19699092

➶

reach

"Since the p97, VCIP135, and syntaxin5 complex is very unstable (XREF_FIG C), a tighter VCIP135 and p97 complex then dissociates from syntaxin5 (XREF_FIG F)."

12473691

➶

reach

"However, the VCIP135, p97, p47, GST, and syn5DeltaTM complex was dissociated only in the presence of ATP (XREF_FIG E, lane 4), and the VCIP135 and p97 complex was observed in the supernatant (unpublished data)."

12473691

➶

reach

"This provides a reasonable explanation for our biochemical data that p47 (271-370) binds to p97 but not to the p97 and VCIP135 complex (XREF_FIG B)."

12473691

GEMIN4 binds PLEK and VCPIP1. 3 / 3

| 3

➶

reach

"However, it has also been shown that ATP is required for the p97, p47, and VCIP135 complex to dissociate from Syn5 [XREF_BIBR]."

28819009

➶

reach

"Other studies have confirmed that the p97, p47, and VCIP135 complex is required for cell-cycle-dependent reformation of the ER network and that p97-p47-mediated reassembly of Golgi cisternae requires the deubiquitinating activity of VCIP135 [XREF_BIBR, XREF_BIBR]."

18687060

➶

reach

"The ubiquitin moieties on these substrates, added by HACE1 during mitosis, likely serve as receptors for the p97, p47, and VCIP135 complex at the end of mitosis to carry on fusion reactions after the removal of the ubiquitin tags by VCIP135 (XREF_FIG) XREF_BIBR, XREF_BIBR."

23453991

Phosphorylated VCPIP1 binds GEMIN4. 1 / 1

| 1

➶

reach

"We therefore investigated the effect of phosphorylation on the binding of VCIP135 to p97 or WAC.We first tested whether phosphorylated VCIP135 binds to p97."

23500464

GEMIN4 binds VCPIP1 and STX5. 1 / 1

| 1

➶

reach

"Since the p97, VCIP135, and syntaxin5 complex is very unstable (XREF_FIG C), a tighter VCIP135 and p97 complex then dissociates from syntaxin5 (XREF_FIG F)."

12473691

| 4

VCPIP1 activates GEMIN4. 4 / 4

| 4

➶

reach

"As shown in XREF_FIG G, VCIP135 partially prevented alpha-SNAP binding to GST-syn5DeltaTM, suggesting that VCIP135 directs syntaxin5 to p97 and p47 but not to alpha-SNAP and NSF."

12473691

➶

reach

"Next, we wanted to ascertain whether VCIP135 contributes to p97 and p47 mediated membrane fusion using an in vitro Golgi reassembly assay."

12473691

➶

reach

"The deubiquitinase VCIP135, which is associated with the p97 and p47 complex, removes the ubiquitin moiety and thus allows p97 and p47 to fuse the membranes after mitosis (XREF_FIG) 37."

23453991

➶

reach

"Considering that the disassembly of the p97, p47, and SNARE complex by VCIP135 requires ATP hydrolysis (XREF_FIG E), we suggest that the function of VCIP135 in membrane fusion is to mediate the dissociation of the p97, p47, and SNARE complex, which may be part of the SNARE priming process."

12473691

VCPIP1 inhibits GEMIN4.

| 3

VCPIP1 inhibits GEMIN4. 3 / 3

| 3

➶

reach

"During mitosis, Cdk1 phosphorylates p47, p37 and VCIP135, and blocks p97 controlled membrane-fusion processes so that the Golgi membranes remain disassembled."

26734607

➶

reach

"In the presence of ATP, the addition of VCIP135 prevented p97 and p47 from binding to syntaxin5 and VCIP135 itself only bound poorly to syntaxin5 (XREF_FIG D, left three lanes)."

12473691

➶

reach

"Our in vitro Golgi reassembly assay confirmed that VCIP135 phosphorylation at S130 attenuates p97 and p47 mediated Golgi membrane fusion (XREF_FIG)."

25904330

X affects VCPIP1

| 11 11

X binds VCPIP1. 10 / 22

| 11 11

➶

sparser

"The GST pulldown assay demonstrated that VCPIP1 bound to HBx directly ( xref ) in vitro ."

35695579

➶

sparser

35695579

➶

sparser

"These results demonstrate that the interaction between HBx and VCPIP1 may increase HBx stability."

35695579

➶

sparser

39494904

➶

sparser

"We, therefore, tested whether these domains were involved in VCPIP1-HBx binding."

39494904

➶

sparser

"The mutual interactions between VCPIP1 and HBx ( xref ), HBx and PSMC3 ( xref ), and PSMC3 and VCPIP1 ( xref ) were identified."

35695579

➶

sparser

35695579

➶

sparser

35695579

➶

sparser

35695579

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reach

35695579

WAC affects VCPIP1

4 | 1 6 7

WAC binds VCPIP1. 10 / 15

4 | 1 4 5

➶

sparser

"In this study, we isolated a VCIP135 mutant, VCIP135(T760E, S767E), that still binds to WAC and maintains its deubiquitinating enzyme activity, but lacks p97-binding affinity."

23500464

➶

reach

"Furthermore, VCIP135 interacts with WAC, which enhances the DUB activity of VCIP135."

23453991

➶

reach

"Golgi WAC interacts with the deubiquitinase VCIP135, which binds VCP and p97."

26687599

➶

sparser

"Furthermore, VCIP135 interacts with WAC, which enhances the DUB activity of VCIP135."

23453991

➶

biogrid

No evidence text available

23500464

➶

reach

"WAC directly binds to VCIP135 and increases its deubiquitinating activity."

21811234

➶

sparser

"WAC directly binds to VCIP135 and increases its deubiquitinating activity."

21811234

➶

sparser

"WAC binds to VCIP135, mediating its association with the Golgi, and activating its deubiquitinating function to regulate Golgi biogenesis ( xref )."

26812014

➶

reach

"WAC binds to VCIP135, mediating its association with the Golgi, and activating its deubiquitinating function to regulate Golgi biogenesis."

26812014

➶

biogrid

No evidence text available

21811234

P97 binds WAC and VCPIP1. 1 / 1

| 1

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sparser

"We therefore investigated the effect of phosphorylation on the binding of VCIP135 to p97 or WAC."

23500464

VCPIP1-S767E binds WAC. 1 / 1

| 1

➶

reach

"In this study, we isolated a VCIP135 mutant, VCIP135 (T760E, S767E), that still binds to WAC and maintains its deubiquitinating enzyme activity, but lacks p97 binding affinity."

23500464

VCPIP1 binds WAC and GST. 1 / 1

| 1

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sparser

23500464

VCPIP1-T760E binds WAC. 1 / 1

| 1

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reach

"In this study, we isolated a VCIP135 mutant, VCIP135 (T760E, S767E), that still binds to WAC and maintains its deubiquitinating enzyme activity, but lacks p97 binding affinity."

23500464

VCPIP1 affects PLEK

| 17

VCPIP1 binds PLEK.

| 11

VCPIP1 binds PLEK. 6 / 6

| 6

➶

reach

"Although the nature of the ubiquitinated proteins as well as how the p97–p47-VCIP135 complex acts on these molecules during Golgi reassembly remains to be determined, the new findings have revealed a [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16529947

➶

reach

"During late mitosis, VCIP135 becomes dephosphorylated and associates with the p97, p47, and Syn5 complex."

28819009

➶

reach

"The p97 and p47 binding protein VCIP135 (VCP [p97] and p47 complex interacting protein, p135) functions as a deubiquitinating enzyme whose activity is required for post-mitotic Golgi reassembly 26."

29225785

➶

reach

"VCIP135 binds to the p97, p47, and syntaxin-5 complex and can dissociate p97 and p47 from syntaxin-5."

15037600

➶

reach

"We have shown that VCIP135 binds to syntaxin5 and disassembles the p97, p47, and syntaxin5 complex through p97 ATP hydrolysis."

12473691

➶

reach

"VCIP135 binds to the p97/p47/syntaxin5 complex and promotes its dissociation via p97 catalysed ATP hydrolysis ( Uchiyama et al., 2002 )."

14643202

GEMIN4 binds PLEK and VCPIP1. 3 / 3

| 3

➶

reach

"However, it has also been shown that ATP is required for the p97, p47, and VCIP135 complex to dissociate from Syn5 [XREF_BIBR]."

28819009

➶

reach

18687060

➶

reach

23453991

VCP binds PLEK and VCPIP1. 1 / 1

| 1

➶

reach

"Fusion of membrane tubules also requires NSF/α, γ-SNAP, the p97/p47/VCIP135 complex, syntaxin 18, and BNIP1/sec20 [11] ."

21215635

VCPIP1 binds GEMIN4, PLEK, GST, and syn5DeltaTM. 1 / 1

| 1

➶

reach

12473691

VCPIP1 activates PLEK.

| 4

VCPIP1 activates PLEK. 4 / 4

| 4

➶

reach

"Next, we wanted to ascertain whether VCIP135 contributes to p97 and p47 mediated membrane fusion using an in vitro Golgi reassembly assay."

12473691

➶

reach

"As shown in XREF_FIG G, VCIP135 partially prevented alpha-SNAP binding to GST-syn5DeltaTM, suggesting that VCIP135 directs syntaxin5 to p97 and p47 but not to alpha-SNAP and NSF."

12473691

➶

reach

"In particular, as p47, p37, Ufd1, and VCIP135 share the same p97-binding motif (SHP motif), it is reasonable that VCIP135 may induce the dissociation of complexes of p97 with p47, p37, and Ufd1."

38072049

➶

reach

"The deubiquitinase VCIP135, which is associated with the p97 and p47 complex, removes the ubiquitin moiety and thus allows p97 and p47 to fuse the membranes after mitosis (XREF_FIG) 37."

23453991

VCPIP1 inhibits PLEK.

| 2

VCPIP1 inhibits PLEK. 2 / 2

| 2

➶

reach

"Our in vitro Golgi reassembly assay confirmed that VCIP135 phosphorylation at S130 attenuates p97 and p47 mediated Golgi membrane fusion (XREF_FIG)."

25904330

➶

reach

"In the presence of ATP, the addition of VCIP135 prevented p97 and p47 from binding to syntaxin5 and VCIP135 itself only bound poorly to syntaxin5 (XREF_FIG D, left three lanes)."

12473691

MYBL1 affects VCPIP1

| 2 14

MYBL1 binds VCPIP1.

| 14

VCPIP1 binds MYBL1. 10 / 14

| 14

➶

sparser

"MYB was rearranged in 60% (12/20), MYBL1 in 30% (6/20) and NFIB in 5% (1/20); two tumors exhibited novel fusion products, including NFIB-TBPL1 and MYBL1-VCPIP1 ."

34176176

➶

sparser

"However, Bubola et al. [ xref ] identified a MYBL1-VCPIP1 fusion product following the genomic characterization of salivary gland tumors."

39796135

➶

sparser

"The VCPIP1 gene is particularly interesting to our research because it is (a) downregulated when we silence MYBL1 in MDA-MB-231 cells, (b) it is located at the 8q13.1 chromosomal locus, like MYBL1, (c) it is dysregulated in many of the same TNBC patient samples as MYBL1, (d) bioinformatic analyses indicate MYBL1 transcription factor protein binding to the VCPIP1 gene, and (e) both genes are involved in cell cycle signaling mechanisms."

39796135

➶

sparser

"In addition, two cases were found to harbor novel fusion genes ( NFIB-TBPL1 and MYBL1-VCPIP1 )."

34176176

➶

sparser

"It could be, but we are examining the possibility that the MYBL1 transcription factor directly binds to VCPIP1 promoter allowing for direct regulation in TNBC."

38473786

➶

sparser

"The Electrophoretic Mobility Shift Assay (EMSA) is performed to show that the MYBL1 transcription factor can bind to the promoter region of the VCPIP1 gene."

39796135

➶

sparser

"In contrast, other than the identification of a MYBL1-VCPIP1 gene fusion event in salivary gland tumors [ xref ], a possible relationship between MYBL1 and VCPIP1 genes has not been established."

39796135

➶

sparser

"Adenoid cystic carcinoma is characterized by a recurrent t(6;9)(q22–23;p23–24) translocation that results in a MYB-NFIB fusion gene. xref , xref An alternative MYBL1-NFIB gene fusion has been reported in a subset of cases. xref , xref , xref Various other genes have been reported to substitute for MYB , MYBL1 and NFIB , including TGFRB3, RAD51B, YTHDF3, AIG1, XRCC4 and PTPRD , amongst others. xref , xref , xref – xref In our cohort of 20 AdCCs, the MYB-NFIB fusion was identified in 60% and the MYBL1-NFIB fusion in 25%, while two cases harbored novel NFIB-TBPL1 and MYBL1-VCPIP1 fusions products."

34176176

➶

sparser

"Co-Expression of MYBL1 and VCPIP1 Genes and Experimental Analyses of MYBL1 Transcription Factor Binding to VCPIP1 Promoter."

39796135

➶

sparser

"In addition, because bioinformatic analyses suggest the possible regulation of VCPIP1 by the MYBL1 transcription factor, we decided to experimentally examine the possibility that MYBL1 binds directly to the VCPIP1 promoter region, explaining our previous gene expression results."

39796135

MYBL1 increases the amount of VCPIP1.

| 2

MYBL1 increases the amount of VCPIP1. 2 / 2

| 2

➶

reach

"These results imply that miR-145-3p regulates COX1 and COX2 genes, which possibly associates with mitochondrial activity.We subsequently knocked down MYBL1 and found that deficiency of MYBL1 in proliferating MuSCs decreased the expression of VCPIP1, Vexin, and COX1, while that of COX2 was increased (Figure 6F), which exactly mimics the inhibitory effect of ectopic miR-145-3p on these genes."

37176056

➶

reach

"MYBL1 Mediates the Regulation of miR-145-3p on Expression of Vexin, VCPIP1, COX1, and COX2."

37176056

SPRTN affects VCPIP1

5 | 6 4

SPRTN binds VCPIP1.

5 | 5 4

SPRTN binds VCPIP1. 10 / 14

5 | 5 4

➶

sparser

"Moreover, after treating cells with three known DPC-inducing agents, FA, camptothecin (CPT) and cisplatin ( xref ), the interaction between VCPIP1 and SPRTN increased ( xref and xref – xref )."

32649882

➶

reach

32649882

➶

sparser

"Our data strongly suggest that VCPIP1-SPRTN signaling axis is the key regulation in DPC repair."

32649882

➶

sparser

"As VCPIP1-SPRTN signaling protects cells from DPC induction, it seems likely that inhibition of VCPIP1-SPRTN could be employed to sensitize cells to different kinds of DPC-inducing agents."

32649882

➶

reach

"Knockdown of VCP did not change the SPRTN/VCPIP1 interaction (Figure S2J)."

32649882

➶

biogrid

No evidence text available

32649882

➶

biogrid

No evidence text available

32649882

➶

biogrid

No evidence text available

32649882

➶

biogrid

No evidence text available

32649882

➶

reach

"VCPIP1 and USP11 interact weakly with SPRTN in co-immunoprecipitating experiments, but show no (VCPIP1) or only weak (USP11) preference for SPRTN-Ub (XREF_SUPPLEMENTARY)."

33348378

SPRTN activates VCPIP1.

| 1

SPRTN activates VCPIP1. 1 / 1

| 1

➶

reach

"Upon DPC induction, the deubiquitinase VCPIP1/VCIP135 is activated by ATM/ATR, which then deubiquitinates SPRTN."

32649882

VCPIP1 affects MYBL1

| 14

VCPIP1 binds MYBL1. 10 / 14

| 14

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sparser

"MYB was rearranged in 60% (12/20), MYBL1 in 30% (6/20) and NFIB in 5% (1/20); two tumors exhibited novel fusion products, including NFIB-TBPL1 and MYBL1-VCPIP1 ."

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"However, Bubola et al. [ xref ] identified a MYBL1-VCPIP1 fusion product following the genomic characterization of salivary gland tumors."

39796135

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39796135

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"In addition, two cases were found to harbor novel fusion genes ( NFIB-TBPL1 and MYBL1-VCPIP1 )."

34176176

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"It could be, but we are examining the possibility that the MYBL1 transcription factor directly binds to VCPIP1 promoter allowing for direct regulation in TNBC."

38473786

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"The Electrophoretic Mobility Shift Assay (EMSA) is performed to show that the MYBL1 transcription factor can bind to the promoter region of the VCPIP1 gene."

39796135

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"In contrast, other than the identification of a MYBL1-VCPIP1 gene fusion event in salivary gland tumors [ xref ], a possible relationship between MYBL1 and VCPIP1 genes has not been established."

39796135

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"Co-Expression of MYBL1 and VCPIP1 Genes and Experimental Analyses of MYBL1 Transcription Factor Binding to VCPIP1 Promoter."

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39796135

VCPIP1 affects SNTG2

2 1 | 8 2

VCPIP1 deubiquitinates SNTG2.

1 | 6

VCPIP1 deubiquitinates SNTG2. 7 / 7

1 | 6

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"Syn5 is monoubiquitinated by the ubiquitin ligase HACE1 in early mitosis and deubiquitinated by the deubiquitinase VCIP135 in late mitosis."

27404360

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"One possible explanation, as described in our model (XREF_FIG), is that monoubiquitination of Syn5 occurs only transiently in early mitosis and is quickly reversed by the deubiquitinase VCIP135 in late mitosis."

27404360

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"In late mitosis, the DUB VCIP135, which associates with p97 via its UBX-L (UBX like) domain, deubiquitinates Syn5, which permits interaction between the SNAREs, membrane fusion and finally the formation of Golgi cisternae [XREF_BIBR]."

28819009

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reach

"Therefore, we determined whether Syn5 is deubiquitinated by VCIP135."

27404360

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reach

"These results suggest that Syn5 is deubiquitinated by VCIP135."

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VCPIP1 activates SNTG2. 2 / 2

| 2

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"In late mitosis, VCIP135 is reactivated by dephosphorylation, removes ubiquitin from Syn5, and allows Syn5 interacting with its cognate SNARE Bet1 for membrane fusion at mitotic exit (XREF_FIG, right panel)."

27404360

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reach

"To investigate whether ubiquitinated Syn5 is a direct substrate of VCIP135, in vitro ubiquitinated Syn5 was treated with recombinant VCIP135."

27404360

PLEK affects VCPIP1

| 12

PLEK binds VCPIP1.

| 11

VCPIP1 binds PLEK. 6 / 6

| 6

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reach

16529947

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"During late mitosis, VCIP135 becomes dephosphorylated and associates with the p97, p47, and Syn5 complex."

28819009

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"The p97 and p47 binding protein VCIP135 (VCP [p97] and p47 complex interacting protein, p135) functions as a deubiquitinating enzyme whose activity is required for post-mitotic Golgi reassembly 26."

29225785

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"VCIP135 binds to the p97, p47, and syntaxin-5 complex and can dissociate p97 and p47 from syntaxin-5."

15037600

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"We have shown that VCIP135 binds to syntaxin5 and disassembles the p97, p47, and syntaxin5 complex through p97 ATP hydrolysis."

12473691

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reach

"VCIP135 binds to the p97/p47/syntaxin5 complex and promotes its dissociation via p97 catalysed ATP hydrolysis ( Uchiyama et al., 2002 )."

14643202

GEMIN4 binds PLEK and VCPIP1. 3 / 3

| 3

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reach

"However, it has also been shown that ATP is required for the p97, p47, and VCIP135 complex to dissociate from Syn5 [XREF_BIBR]."

28819009

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18687060

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23453991

VCP binds PLEK and VCPIP1. 1 / 1

| 1

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reach

"Fusion of membrane tubules also requires NSF/α, γ-SNAP, the p97/p47/VCIP135 complex, syntaxin 18, and BNIP1/sec20 [11] ."

21215635

VCPIP1 binds GEMIN4, PLEK, GST, and syn5DeltaTM. 1 / 1

| 1

➶

reach

12473691

PLEK activates VCPIP1.

| 1

PLEK activates VCPIP1. 1 / 1

| 1

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reach

"WAC is hence thought to function in p97 and p47 mediated Golgi membrane fusion by activating the deubiquitinating function of VCIP135."

21811234

P47 affects VCPIP1

| 10

P47 binds VCPIP1. 5 / 5

| 5

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"The inhibition of p97 ATPase activity can be reduced if both p47-binding sites are not occupied, and the metastable complex of VCIP135/p97/p47 would represent such a case: VCIP135 interacts with the p97/p47 complex that uses only one p47-binding site."

12473691

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"Several lines of recent evidence suggest that ubiquitination may be implicated in the p97/p47 pathway; p47 binds to monoubiquitinated proteins and VCIP135 shows a deubiquitinating activity in vitro."

15749824

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"As ATPases, NSF and p97 have specific co-factors: NSF-mediated fusion requires the proteins SNAPs and p115, while the p97-mediated pathway requires formation of a complex with p47 and VCIP135, or with p37 (Kondo et al., xref ; Uchiyama et al., xref )."

26734607

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"However, it was proposed that the DUB VCIP135 forms an unstable ternary complex with p97 p47 during post-mitotic Golgi reassembly, where p47 would be associated with p97 via only one of its two bindin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26320413

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"VCIP135 cannot interact with p47 directly ( xref A)."

12473691

VCPIP1 binds SNTG2, p47, and p97. 2 / 2

| 2

➶

sparser

"During late mitosis, VCIP135 becomes dephosphorylated and associates with the p97–p47–Syn5 complex."

28819009

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sparser

"At this time VCIP135 is inactivated by mitotic phosphorylation ( xref ; xref ) and thus monoubiquitinated Syn5, p97, p47, and VCIP135 form a transient quaternary complex ( xref )."

27404360

VCPIP1 binds STX5, p97, and p47. 2 / 2

| 2

➶

sparser

"This simple binding experiment showed that VCIP135 can form a quaternary complex with syntaxin5, p97, and p47 (Fig. S2 available at)."

12473691

➶

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"VCIP135 binds to the p97–p47–syntaxin-5 complex and can dissociate p97 and p47 from syntaxin-5 ( xref )."

15037600

P47 binds p97 and VCPIP1. 1 / 1

| 1

➶

sparser

"Hence, VCIP135 could bind to the p97/p47 complex in cytosol, possibly forming an unstable complex of p47, p97, and VCIP135 that was captured after chemical cross-linking."

12473691

VCPIP1 affects Deubiquitinase

| 4

VCPIP1 inhibits Deubiquitinase.

| 3

VCPIP1 inhibits Deubiquitinase. 3 / 6

| 3

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"Mitotic phosphorylation of VCIP135 at S130 inhibits its deubiquitinase activity."

25904330

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reach

"In this study, we found that phosphorylation of VCIP135 at a single site, S130, is necessary and sufficient to inactivate its DUB activity for Golgi disassembly in early mitosis."

25904330

➶

reach

25904330

VCPIP1 activates Deubiquitinase.

| 1

VCPIP1 activates Deubiquitinase. 1 / 2

| 1

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reach

"Dephosphorylation of S130 on VCIP135 upon staurosporine or roscovitine but not U0126 treatment also significantly increased the DUB activity of endogenous VCIP135 (XREF_FIG), consistent with the hypothesis that phosphorylation at S130 inactivates VCIP135."

25904330

NSFL1C affects VCPIP1

4 1 | 1

NSFL1C binds VCPIP1.

4 1 |

VCPIP1 binds NSFL1C. 4 / 4

4 |

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No evidence text available

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No evidence text available

26389662

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No evidence text available

19615732

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No evidence text available

sparser

"These results demonstrate that VCIP135 S130 phosphorylation regulates its DUB activity."

25904330

➶

sparser

"VCIP135 S130 phosphorylation in the cell cycle."

25904330

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4 |

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ctd

No evidence text available

30816183

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No evidence text available

29097150

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No evidence text available

25181051

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No evidence text available

34947998

Bisphenol A decreases the amount of VCPIP1.

1 |

Bisphenol A decreases the amount of VCPIP1. 1 / 1

1 |

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ctd

No evidence text available

31675489

VCPIP1 affects NSFL1C

4 1 |

VCPIP1 binds NSFL1C. 4 / 4

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No evidence text available

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No evidence text available

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No evidence text available

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No evidence text available

18775313

VCP binds STX5, NSFL1C, and VCPIP1. 1 / 1

1 |

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No evidence text available

12473691

VCPIP1 affects MAF1

3 | 2

MAF1 binds VCPIP1. 5 / 5

3 | 2

➶

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"The MAF1 gene is relevant because several different interactome analyses demonstrate VCPIP1 and MAF1 protein:protein interactions [ xref ] ((accessed on 25 June 2024))."

39796135

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"Summarized in the STRING TM analyses [ xref ], Interactome data demonstrate protein:protein interactions between VCPIP1 and MAF1, and the Reactome database shows evidence of interactions between the MAF1 and RBBP4 genes ( xref )."

39796135

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No evidence text available

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No evidence text available

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No evidence text available

28514442

VCPIP1 affects GST

| 2 3

VCPIP1 binds GST. 2 / 2

| 1 1

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"Briefly, GST-VCIP135(F1024L/L1031P), which binds to the C-terminus of p97 but not to its N-terminus, was incubated with p97, and immobilized onto GSH-beads."

38072049

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reach

"20 µL pre‐equilibrated glutathione Sepharose 4B resin (GE Healthcare) was applied to each reaction mixture to pellet the P97/VCP and GST‐VCPIP1 complexes."

39234822

VCPIP1 binds GEMIN4, PLEK, GST, and syn5DeltaTM. 1 / 1

| 1

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reach

12473691

VCPIP1 binds WAC and GST. 1 / 1

| 1

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23500464

VCPIP1 binds p97 and GST. 1 / 1

| 1

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sparser

"Much less VCIP135(T760E, S767E) bound to GST-p97 ( Fig. 2 B, upper panel, lane 2) compared with VCIP135wt (lane 1)."

23500464

VCPIP1 affects DNA-templated transcription

| 5

VCPIP1 activates DNA-templated transcription. 5 / 5

| 5

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"We also demonstrated that VCPIP1 overexpression promoted the HBV cccDNA transcription and enhanced the HBV gene expression in the HBV-infected HepG2-NTCP cells."

35695579

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"By using a series of HBV replication and infection models, we extensively characterized VCPIP1-mediated upregulation of HBV transcription, antigen expression, and genome replication."

39494904

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reach

"VCPIP1 enhances HBV transcription, antigen expression, and genome replication."

39494904

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reach

"In the recent report by Wu et al., overexpression of VCPIP1 and/or PSMC3 was also shown to cause increased HBV transcription, antigen secretion, and progeny virus production in infected HepG2-NTCP cells."

39494904

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reach

"The recent report by Wu et al. also showed that overexpression of VCPIP1 and/or PSMC3 increased HBV transcription, antigen secretion, and progeny virus production in infected HepG2-NTCP cells (17)."

39494904

MAF1 affects VCPIP1

3 | 2

MAF1 binds VCPIP1. 5 / 5

3 | 2

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"The MAF1 gene is relevant because several different interactome analyses demonstrate VCPIP1 and MAF1 protein:protein interactions [ xref ] ((accessed on 25 June 2024))."

39796135

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39796135

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No evidence text available

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No evidence text available

28514442

GST affects VCPIP1

| 2 3

VCPIP1 binds GST. 2 / 2

| 1 1

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"Briefly, GST-VCIP135(F1024L/L1031P), which binds to the C-terminus of p97 but not to its N-terminus, was incubated with p97, and immobilized onto GSH-beads."

38072049

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reach

"20 µL pre‐equilibrated glutathione Sepharose 4B resin (GE Healthcare) was applied to each reaction mixture to pellet the P97/VCP and GST‐VCPIP1 complexes."

39234822

VCPIP1 binds GEMIN4, PLEK, GST, and syn5DeltaTM. 1 / 1

| 1

➶

reach

12473691

VCPIP1 binds WAC and GST. 1 / 1

| 1

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23500464

VCPIP1 binds p97 and GST. 1 / 1

| 1

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sparser

"Much less VCIP135(T760E, S767E) bound to GST-p97 ( Fig. 2 B, upper panel, lane 2) compared with VCIP135wt (lane 1)."

23500464

ATM affects VCPIP1

| 5

ATM phosphorylates VCPIP1.

| 4

ATM phosphorylates VCPIP1. 4 / 4

| 4

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"Here, we report that in response to DPC induction, the deubiquitinase VCPIP1/VCIP135 is phosphorylated and activated by ATM/ATR."

32649882

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"Taken together, these data suggest that VCPIP1 phosphorylation by ATM/ATR is important for VCPIP1 activation following DPC induction."

32649882

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reach

"VCPIP1 is phosphorylated by ATM/ATR upon DPC induction."

32649882

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reach

"These results suggest that VCPIP1 is phosphorylated by ATM/ATR following DPC induction."

32649882

ATM activates VCPIP1.

| 1

ATM activates VCPIP1. 1 / 1

| 1

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reach

"VCPIP1 is activated and shuttled to the nucleus by ATM/ATR-mediated phosphorylation, where it can remove the Ub mark, enabling SPRTN recruitment to chromatin and downstream repair of the DPC."

38572758

Rep affects VCPIP1

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Rep binds VCPIP1. 4 / 4

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No evidence text available

34672954

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No evidence text available

| DOI

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No evidence text available

| DOI

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No evidence text available

| DOI

VCPIP1

| DOI

➶

| 4

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reach

"Although VCPIP1 overexpression led to significantly increased HBx in the Huh7 and HepG2 cells, it did not redice the amounts of HBx ubiquitination (Fig. 4C)."

35695579

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"As expected, ectopic VCPIP1 expression led to significantly increased HBx in a dose-dependent manner in both Huh7 and HepG2 cells (Fig. 2B)."

35695579

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"The dual-luciferase reporter assay showed that further VCPIP1 expression significantly enhanced the HBx-induced transactivation activity of NF-κB, AP-1, and SP-1 in the Huh7 and HepG2 cells, whereas VCPIP1 alone had no such effects (Fig. 7A)."

35695579

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reach

"In addition, double knockdown of MATIIα and VCIP135 dramatically inhibits the growth in Huh7 and MHCC-97H cells (Fig. 5g and Supplementary Fig. S6c)."

35729157

VCPIP1 affects MAT2A

1 | 3

VCPIP1 binds MAT2A.

1 | 1

VCPIP1 binds MAT2A. 2 / 2

1 | 1

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reach

"Here, we identified that VCIP135 binds to MATIIα to enhance MATIIα protein stability via deubiquitylation in response to folate treatment."

| 2

➶

sparser

"During late mitosis, VCIP135 becomes dephosphorylated and associates with the p97–p47–Syn5 complex."

28819009

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sparser

"At this time VCIP135 is inactivated by mitotic phosphorylation ( xref ; xref ) and thus monoubiquitinated Syn5, p97, p47, and VCIP135 form a transient quaternary complex ( xref )."

27404360

SNTG2 binds VCPIP1. 2 / 2

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No evidence text available

27404360

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No evidence text available

27404360

PLEK affects GEMIN4

| 4

GEMIN4 binds PLEK and VCPIP1. 3 / 3

| 3

➶

reach

"However, it has also been shown that ATP is required for the p97, p47, and VCIP135 complex to dissociate from Syn5 [XREF_BIBR]."

28819009

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18687060

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23453991

VCPIP1 binds GEMIN4, PLEK, GST, and syn5DeltaTM. 1 / 1

| 1

➶

reach

12473691

ATR affects VCPIP1

| 4

ATR phosphorylates VCPIP1. 4 / 4

| 4

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reach

"These results suggest that VCPIP1 is phosphorylated by ATM/ATR following DPC induction."

32649882

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reach

"VCPIP1 is phosphorylated by ATM/ATR upon DPC induction."

32649882

➶

reach

"Taken together, these data suggest that VCPIP1 phosphorylation by ATM/ATR is important for VCPIP1 activation following DPC induction."

32649882

➶

| 2

➶

sparser

"This simple binding experiment showed that VCIP135 can form a quaternary complex with syntaxin5, p97, and p47 (Fig. S2 available at)."

12473691

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sparser

"VCIP135 binds to the p97–p47–syntaxin-5 complex and can dissociate p97 and p47 from syntaxin-5 ( xref )."

15037600

VCPIP1 binds p97 and STX5. 1 / 1

| 1

➶

sparser

"VCIP135 did not bind to syntaxin5 with p97 ( xref C, lane 4), a finding which was investigated further ( xref F)."

12473691

VCPIP1 affects VCPIP1

| 3

VCPIP1 activates VCPIP1.

| 2

VCPIP1 bound to STX5 activates VCPIP1. 1 / 1

| 1

➶

reach

"The binding of VCIP135 to syntaxin5 independently of p47 (XREF_FIG C) allows VCIP135 to be closely associated with the p97 and p47 complex, whereas in cytosol such an association is less likely."

12473691

VCPIP1 activates VCPIP1. 1 / 1

| 1

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reach

25904330

VCPIP1 increases the amount of VCPIP1.

| 1

VCPIP1 increases the amount of VCPIP1. 1 / 1

| 1

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reach

"Western blotting showed that the VCIP135 siRNA duplex significantly decreased the intracellular level of VCIP135 (Fig. S2A)."

38072049

VCPIP1 affects UFD1

2 | 1

VCPIP1 binds UFD1.

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VCPIP1 binds UFD1. 2 / 2

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No evidence text available

26389662

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No evidence text available

19615732

VCPIP1 activates UFD1.

| 3

VCPIP1 inhibits Top1cc.

| 2

VCPIP1 inhibits Top1cc. 2 / 2

| 2

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reach

"Loss of VCPIP1 resulted in cellular hypersensitivity to DPC-inducing agents, as well as Top1cc and DPC accumulation, suggesting that VCPIP1 plays a critical role in DPC repair."

32649882

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reach

"We found that VCPIP1 deficiency resulted in enhanced Top1cc foci signals after CPT treatment (Figures 1M–1N), suggesting a role of VCPIP1 in Top1cc removal."

32649882

VCPIP1 activates Top1cc.

| 3

VCPIP1 activates Golgi membrane fusion.

| 2

VCPIP1 activates Golgi membrane fusion. 1 / 1

| 1

➶

reach

"The substantial morphological remodeling of the Golgi after mitosis is regulated by P97/VCP‐VCPIP1 mediated Golgi membrane fusion (11, 15, 22, 24)."

sparser

"VCIP135 binds to the p97–p47–syntaxin-5 complex and can dissociate p97 and p47 from syntaxin-5 ( xref )."

15037600

VCPIP1 binds p97 and STX5. 1 / 1

| 1

➶

sparser

"VCIP135 did not bind to syntaxin5 with p97 ( xref C, lane 4), a finding which was investigated further ( xref F)."

12473691

PSMC3 affects VCPIP1

| 3

PSMC3 binds VCPIP1.

| 2

VCPIP1 binds PSMC3. 2 / 2

| 2

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reach

"The mutual interactions between VCPIP1 and HBx (Fig. 1), HBx and PSMC3 (Fig. 5A), and PSMC3 and VCPIP1 (Fig. 5B) were identified."

35695579

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35695579

PSMC3 increases the amount of VCPIP1.

reach

"We found that GST-syn5DeltaTM bound VCIP135 very efficiently (XREF_FIG A, lane 1) compared with GST-syn1DeltaTM (lane 2)."

12473691

➶

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12473691

GEMIN4 affects PLEK, and VCPIP1

| 3

GEMIN4 binds PLEK and VCPIP1. 3 / 3

| 3

➶

reach

"However, it has also been shown that ATP is required for the p97, p47, and VCIP135 complex to dissociate from Syn5 [XREF_BIBR]."

28819009

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23453991

DND1 affects VCPIP1

3 |

DND1 binds VCPIP1. 3 / 3

3 |

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No evidence text available

26186194

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No evidence text available

28514442

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No evidence text available

33961781

Valproic acid affects VCPIP1

2 |

Valproic acid demethylates VCPIP1.

1 |

Valproic acid demethylates VCPIP1. 1 / 1

1 |

➶

ctd

No evidence text available

29154799

Valproic acid decreases the amount of VCPIP1.

ctd

No evidence text available

21641980

➶

2 |

➶

biogrid

No evidence text available

29119051

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No evidence text available

29119051

VCPIP1 affects viral transcription

| 2

VCPIP1 activates viral transcription. 2 / 2

| 2

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"In all these models, exogenous overexpression of VCPIP1 resulted in the elevation of viral transcription, increased production of secreted HBsAg and HBeAg, and more importantly, higher levels of intracellular capsids and capsid-associated progeny HBV DNA (Fig. 2A)."

39494904

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reach

"In Huh7 cells transfected with p1.3HBV(X ) or pCMV-1.1HBV(X ), knockdown of endogenous VCPIP1 expression reduced viral transcription, production of secreted viral antigens, as well as progeny viral genome replication, whereas exogenous expression of VCPIP1 displayed the opposite effects (Fig. 4)."

39494904

VCPIP1 affects cell population proliferation

| 2

VCPIP1 inhibits cell population proliferation.

| 1

VCPIP1 inhibits cell population proliferation. 1 / 1

| 1

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"VCPIP1-stabilized HBx functions as a canonical transactivator and inhibits cell proliferation.."

35695579

VCPIP1 activates cell population proliferation.

biogrid

No evidence text available

18775313

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| 2

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reach

"VCPIP1 upregulates EnI/Xp promoter and enhancer activities."

39494904

➶

reach

"Interestingly, deletion of the OTU domain obliterated VCPIP1-mediated enhancement of EnI/Xp promoter activity but did not affect its upregulation of EnI/Xp enhancer activity (Fig. 5F)."

39494904

VCPIP1 affects ERBIN

| 2

VCPIP1 ubiquitinates ERBIN.

| 1

VCPIP1 ubiquitinates ERBIN. 1 / 1

| 1

➶

reach

"VCPIP1 negatively regulates NF-κB signaling pathways by deubiquitinating and stabilizing Erbin in MDP-stimulated macrophages."

39550842

VCPIP1 increases the amount of ERBIN.

biogrid

No evidence text available

26389662

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| 1

HSPA6 deubiquitinates VCPIP1. 1 / 1

| 1

➶

reach

"Deubiquitinating protein VCIP135, the F-actin-capping protein sub-unit alpha-2, and insulin-like growth factor 2 mRNA-binding protein 2 were biotinylated via AirID fused with OR, RTP1S-AirID biotinylated heat shock protein A6 (HSPA6), and double-stranded RNA-binding protein Staufen homolog 2 (STAU2)."

37175532