Table of Contents
ISRN Molecular Biology
Volume 2013, Article ID 548359, 19 pages
Review Article

The Not4 RING E3 Ligase: A Relevant Player in Cotranslational Quality Control

Department of Microbiology and Molecular Medicine, Faculty of Medicine, CMU, University of Geneva, 1 Rue Michel Servet, 1211 Geneva 4, Switzerland

Received 4 November 2012; Accepted 21 November 2012

Academic Editors: J. Ciesiolka, M. Greenwood, H.-C. Lee, A. Maucuer, and T. O'Connor

Copyright © 2013 Martine A. Collart. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The Not4 RING E3 ligase is a subunit of the evolutionarily conserved Ccr4-Not complex. Originally identified in yeast by mutations that increase transcription, it was subsequently defined as an ubiquitin ligase. Substrates for this ligase were characterized in yeast and in metazoans. Interestingly, some substrates for this ligase are targeted for polyubiquitination and degradation, while others instead are stable monoubiquitinated proteins. The former are mostly involved in transcription, while the latter are a ribosomal protein and a ribosome-associated chaperone. Consistently, Not4 and all other subunits of the Ccr4-Not complex are present in translating ribosomes. An important function for Not4 in cotranslational quality control has emerged. In the absence of Not4, the total level of polysomes is reduced. In addition, translationally arrested polypeptides, aggregated proteins, and polyubiquitinated proteins accumulate. Its role in quality control is likely to be related on one hand to its importance for the functional assembly of the proteasome and on the other hand to its association with the RNA degradation machines. Not4 is in an ideal position to signal to degradation mRNAs whose translation has been aborted, and this defines Not4 as a key player in the quality control of newly synthesized proteins.