A second chance for protein targeting/folding: Ubiquitination and deubiquitination of nascent proteins. (31st March 2022)

• Record Type: Journal Article
• Authors: Culver, Jacob A.; Li, Xia; Jordan, Matthew; Mariappan, Malaiyalam
• Is Part Of: BioEssays. Volume 44:Number 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-31
• Subjects: chaperones -- deubiquitination -- protein folding -- protein misfolding -- protein quality control -- protein unfolding -- tail‐anchored proteins -- ubiquitination; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202200014
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract: Molecular chaperones in cells constantly monitor and bind to exposed hydrophobicity in newly synthesized proteins and assist them in folding or targeting to cellular membranes for insertion. However, proteins can be misfolded or mistargeted, which often causes hydrophobic amino acids to be exposed to the aqueous cytosol. Again, chaperones recognize exposed hydrophobicity in these proteins to prevent nonspecific interactions and aggregation, which are harmful to cells. The chaperone‐bound misfolded proteins are then decorated with ubiquitin chains denoting them for proteasomal degradation. It remains enigmatic how molecular chaperones can mediate both maturation of nascent proteins and ubiquitination of misfolded proteins solely based on their exposed hydrophobic signals. In this review, we propose a dynamic ubiquitination and deubiquitination model in which ubiquitination of newly synthesized proteins serves as a "fix me" signal for either refolding of soluble proteins or retargeting of membrane proteins with the help of chaperones and deubiquitinases. Such a model would provide additional time for aberrant nascent proteins to fold or route for membrane insertion, thus avoiding excessive protein degradation and saving cellular energy spent on protein synthesis. Also see the video abstract here: https://youtu.be/gkElfmqaKG4 Abstract : Nascent proteins are at risk of misfolding, ubiquitination, and proteasomal degradation. However, ubiquitination does not always signify the end for proteins. We propose a model that uses ubiquitination as a "fix me" signal for misfolded nascent proteins. Ubiquitination may recruit unfolding enzymes, deubiquitinases, and chaperones to provide additional chances for aberrant nascent proteins to fold properly.