A cotranslational ubiquitination pathway for quality control of misfolded proteins.

ABSTRACT: Previous studies have indicated that 6%-30% of newly synthesized proteins are rapidly degraded by the ubiquitin-proteasome system; however, the relationship of ubiquitination to translation for these proteins has been unclear. We report that cotranslational ubiquitination (CTU) is a robust process, with 12%-15% of nascent polypeptides being ubiquitinated in human cells. CTU products contained primarily K48-linked polyubiquitin chains, consistent with a proteasomal targeting function. While nascent chains have been shown previously to be ubiquitinated within stalled complexes (CTU(S)), the majority of nascent chain ubiquitination occurred within active translation complexes (CTU(A)). CTU(A) was increased in response to agents that induce protein misfolding, while CTU(S) was increased in res

SUBMITTER: Wang F 

PROVIDER: S-EPMC3654026 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature