C-terminal UBA domains protect ubiquitin receptors by preventing initiation of protein degradation.

Abstract:

:The ubiquitin receptors Rad23 and Dsk2 deliver polyubiquitylated substrates to the proteasome for destruction. The C-terminal ubiquitin-associated (UBA) domain of Rad23 functions as a cis-acting stabilization signal that protects this protein from proteasomal degradation. Here, we provide evidence that the C-terminal UBA domains guard ubiquitin receptors from destruction by preventing initiation of degradation at the proteasome. We show that introduction of unstructured polypeptides that are sufficiently long to function as initiation sites for degradation abrogates the protective effect of UBA domains. Vice versa, degradation of substrates that contain an unstructured extension can be attenuated by the introduction of C-terminal UBA domains. Our study gains insight into the molecular mechanism responsible for the protective effect of UBA domains and explains how ubiquitin receptors can shuttle substrates to the proteasome without themselves becoming subject to proteasomal degradation.

journal_name

Nat Commun

journal_title

Nature communications

authors

Heinen C,Acs K,Hoogstraten D,Dantuma NP

doi

10.1038/ncomms1179

subject

Has Abstract

pub_date

2011-02-08 00:00:00

pages

191

issn

2041-1723

pii

ncomms1179

journal_volume

2

pub_type

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