Proteasome-mediated Cleavage of the Y-box-binding Protein 1 is Linked to DNA-damage Stress Response

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2005 Sep 30

PMID 16193061

Citations 64

Authors

Alexey V Sorokin

Anastasia A Selyutina

Maxim A Skabkin

Sergey G Guryanov

Igor V Nazimov

Christina Richard

John Thng

Jonathan Yau

Poul H B Sorensen

Lev P Ovchinnikov

Valentina Evdokimova

Affiliations

Soon will be listed here.

Abstract

YB-1 is a DNA/RNA-binding nucleocytoplasmic shuttling protein whose regulatory effect on many DNA- and RNA-dependent events is determined by its localization in the cell. Distribution of YB-1 between the nucleus and the cytoplasm is known to be dependent on nuclear targeting and cytoplasmic retention signals located within the C-terminal portion of YB-1. Here, we report that YB-1 undergoes a specific proteolytic cleavage by the 20S proteasome, which splits off the C-terminal 105-amino-acid-long YB-1 fragment containing a cytoplasmic retention signal. Cleavage of YB-1 by the 20S proteasome in vitro appears to be ubiquitin- and ATP-independent, and is abolished by the association of YB-1 with messenger RNA. We also found that genotoxic stress triggers a proteasome-mediated cleavage of YB-1 in vivo and leads to accumulation of the truncated protein in nuclei of stressed cells. Endoproteolytic activity of the proteasome may therefore play an important role in regulating YB-1 functioning, especially under certain stress conditions.

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