Nascent Chain Ubiquitination is Uncoupled from Degradation to Enable Protein Maturation.

ABSTRACT: A significant proportion of nascent proteins undergo polyubiquitination on ribosomes in mammalian cells, yet the fate of these proteins remains elusive. The ribosome-associated quality control (RQC) is a mechanism that mediates the ubiquitination of nascent chains on stalled ribosomes. Here, we find that nascent proteins ubiquitinated on stalled ribosomes by the RQC E3 ligase LTN1 are insufficient for proteasomal degradation. Our biochemical reconstitution studies reveal that ubiquitinated nascent chains are promptly deubiquitinated in the cytosol upon release from stalled ribosomes, as they are no longer associated with LTN1 E3 ligase for continuous ubiquitination to compete with cytosolic deubiquitinases. These deubiquitinated nascent chains can mature into stable proteins. However, if t

SUBMITTER: Li X 

PROVIDER: S-EPMC10592752 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature