Deubiquitinases sharpen substrate discrimination during membrane protein degradation from the ER.

ABSTRACT: Newly synthesized membrane proteins are queried by ubiquitin ligase complexes and triaged between degradative and nondegradative fates. The mechanisms that convert modest differences in substrate-ligase interactions into decisive outcomes of ubiquitination are not well understood. Here, we reconstitute membrane protein recognition and ubiquitination in liposomes using purified components from a viral-mediated degradation pathway. We find that substrate-ligase interactions in the membrane directly influence processivity of ubiquitin attachment to modulate polyubiquitination. Unexpectedly, differential processivity alone could not explain the differential fates in cultured cells of degraded and nondegraded clients. Both computational and experimental analyses identified continuous deubiquiti

SUBMITTER: Zhang ZR 

PROVIDER: S-EPMC3732389 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature