Proteasome-mediated cleavage of the Y-box-binding protein 1 is linked to DNA-damage stress response.
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.
Sorokin
Alexey V
AV
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, Russian Federation.
Selyutina
Anastasia A
AA
Skabkin
Maxim A
MA
Guryanov
Sergey G
SG
Nazimov
Igor V
IV
Richard
Christina
C
Th'ng
John
J
Yau
Jonathan
J
Sorensen
Poul H B
PH
Ovchinnikov
Lev P
LP
Evdokimova
Valentina
V
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D005998:Glycine / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011817:Rabbits; D014407:Tumor Cells, Cultured; D025801:Ubiquitin / Q000378:metabolism; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
D025801:Ubiquitin; D051840:Y-Box-Binding Protein 1; D000255:Adenosine Triphosphate; D004247:DNA; D046988:Proteasome Endopeptidase Complex; D005998:Glycine