IndraLab

Statements

CHMP5 binds USP15. 10 / 10
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"Accordingly, mutations in VCP/p97 that cause IBMPFD (R155H and A232E) disrupt both the physical and functional interaction with CHMP5 and USP15."
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"Collectively, these data suggest that the CHMP5 and USP15 complex suppresses RANK mediated NF-kappaB activation via IkappaBalpha stabilization in osteoclasts, in which mechanism it prevents proteasomal degradation of IkappaBalpha leading to the retention of NF-kappaB in an inactive cytosolic complex."
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"To confirm the observation that the CHMP5 complex in osteoclasts contains the deubiquitinating enzyme USP15 and VCP and p97 (XREF_FIG), the physical interactions between CHMP5, USP15, and VCP and p97 were studied using cell-free immunoprecipitation analysis (XREF_FIG)."
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"Furthermore, immunoprecipitation analysis confirmed that both endogenous and overexpressed CHMP5 interact with USP15, VCP and p97, and beta-Trcp in an osteoclast line and HEK293 cells, respectively (XREF_FIG and unpublished data)."
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"Intriguingly, CHMP5 interacts directly with both USP15 and VCP and p97, whereas there was no direct interaction between USP15 and VCP and p97."
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"To confirm the observation that the CHMP5 complex in osteoclasts contains the deubiquitinating enzyme USP15 and VCP/p97 ( xref ), the physical interactions between CHMP5, USP15, and VCP/p97 were studied using cell-free immunoprecipitation analysis ( xref )."
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"Intriguingly, CHMP5 interacts directly with both USP15 and VCP/p97, whereas there was no direct interaction between USP15 and VCP/p97."
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"This also raises the possibility that VCP and p97 serves an important function to select the substrates targeted by the CHMP5 and USP15 complex for deubiquitination."
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"Therefore, we speculated whether CHMP5 regulates OA progression by binding to USP15 and NF-κB signaling pathway."
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"As expected, our current investigation showed that CHMP5 was capable of binding USP15 to inhibit IκBα ubiquitination, thereby suppressing enhanced apoptosis and ECM degradation induced by IL-1β through NF-κB signaling pathway in OA chondrocytes.Taken together, CHMP5 alleviates OA development by decreasing OA chondrocyte apoptosis and ECM degradation caused by IL-1β via NF-κB signaling pathway (Fig. 8)."
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