Format

Send to

Choose Destination
Mol Cell. 2013 May 9;50(3):379-93. doi: 10.1016/j.molcel.2013.03.010. Epub 2013 Apr 11.

Principles of cotranslational ubiquitination and quality control at the ribosome.

Author information

1
Department of Biology, Stanford University, Stanford, CA 94305, USA.

Abstract

Achieving efficient cotranslational folding of complex proteomes poses a challenge for eukaryotic cells. Nascent polypeptides that emerge vectorially from the ribosome often cannot fold stably and may be susceptible to misfolding and degradation. The extent to which nascent chains are subject to cotranslational quality control and degradation remains unclear. Here, we directly and quantitatively assess cotranslational ubiquitination and identify, at a systems level, the determinants and factors governing this process. Cotranslational ubiquitination occurs at very low levels and is carried out by a complex network of E3 ubiquitin ligases. Ribosome-associated chaperones and cotranslational folding protect the majority of nascent chains from premature quality control. Nonetheless, a number of nascent chains whose intrinsic properties hinder efficient cotranslational folding remain susceptible for cotranslational ubiquitination. We find that quality control at the ribosome is achieved through a tiered system wherein nascent polypeptides have a chance to fold before becoming accessible to ubiquitination.

Comment in

PMID:
23583075
PMCID:
PMC3886275
DOI:
10.1016/j.molcel.2013.03.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center