%0 Journal Article
%T The Not4 RING E3 Ligase: A Relevant Player in Cotranslational Quality Control
%A Martine A. Collart
%J ISRN Molecular Biology
%D 2013
%R 10.1155/2013/548359
%X 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. 1. Introduction The appropriate control of gene expression is essential to the development and growth of all organisms. Ultimately, gene expression is the production of functional proteins at the appropriate time and level, in their appropriate cellular localization and state for interaction with their correct physiological partners. Many things can go wrong between transcription of a gene and this ultimate goal. Sophisticated surveillance mechanisms have therefore evolved to follow gene expression at every step and destroy aberrant products whose accumulation can be toxic, leading ultimately to cell death. Proteins mediate almost all cellular functions. Hence one crucial step in the expression of a gene is the synthesis of its encoded polypeptide at the ribosome. This process involves many interactions, constraints, modifications, and precisely defined kinetics of synthesis. Multiple quality control systems ensure that the newly synthesized proteins ultimately achieve their native functional form, or if they do not, they get removed and destroyed. This paper will summarize the different components that contribute to this quality control system and present a new and relevant player, the Not4 RING E3 ligase. 2. Folding of Newly Synthesized Polypeptides
%U http://www.hindawi.com/journals/isrn.molecular.biology/2013/548359/