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Statements

USP13 binds EGFR. 10 / 10
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"We then recapitulated the interaction between exogenous USP13 and EGFR in HEK293T cells."
33210294
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"The interaction of wild‐type EGFR with USP13 was hardly detectable, whereas USP13 coimmunoprecipitated with the EGFR ΔE746‐A750 and L858R mutants (Figure xref ), indicating that USP13 associates much more tightly with mutant than wild‐type EGFR."
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"By employing the USP13‐C345A mutant or versions mutated in UBA1, UBA2 or both, we established that the UBA domains' integrity is necessary for USP13 to bind to mutant EGFR (Figure xref )."
33210294
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"We then recapitulated the interaction between exogenous USP13 and EGFR in HEK293T cells."
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"The fraction of mutant EGFR bound to USP13 was also enriched in those two types of ubiquitin chains (Figure xref )."
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"We found that USP13 inhibits mutant EGFR degradation by a process that leads to the accumulation of ubiquitinated (K48 and K63) EGFR, which is bound to c-Cbl and USP13."
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"The association is dependent on the presence of c‐Cbl, as we observed that increased expression of c‐Cbl enhanced USP13‐mutant EGFR interaction."
33210294
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"The isopeptidase‐independent mechanism of action proposed so far for USP13 relies on its UBA domains, which bind to ubiquitinated substrates, possibly inducing structural changes that stabilize them. xref Coincidentally, K63‐linked ubiquitin chains are required for EGFR sorting and degradation. xref This type of chains has also been reported as the preferred substrates for the USP13 UBA domains. xref We found that the UBA domains of USP13 were required for the binding to and stabilizing EGFR, as mutated UBA domains in USP13 resulted in a loss of USP13‐EGFR interaction and of EGFR stabilization."
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"Moreover, degradation of mutant EGFR, mediated by the ubiquitination system, is inhibited by this enzyme, resulting in an accumulation of polyubiquitinated-EGFR bound to USP13."
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"USP13 binds more tightly to the mutant EGFR than to wild-type EGFR."
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