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

Figure 5

Model for the function of Not4 in quality control of newly synthesized proteins. After ribosome stalling in response to a problem in nascent protein folding or mRNA quality, the Ltn1 E3 ligase ubiquitinates the arrested peptide; Not4 is present at the ribosome and can favor proteasome assembly at the ribosome to degrade the ubiquitinated peptide and/or lead to activation of the Ccr4 deadenylase. Its ubiquitination of Rps7A in proximity to translation initiation factors might impact on translation repression, and its ubiquitination of NAC with its UBA domain might impact on the interaction of NAC with the ubiquitinated polypeptide that can be degraded by the proteasome, interact with other chaperones, or instead accumulate in protein aggregates.