Abstract
The Y-box binding protein 1 (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. We have shown previously that YB-1 is cleaved by 20S proteasome between E219 and G220, and the truncated N-terminal YB-1 fragment accumulates in the nuclei of cells treated with DNA damaging drugs. We proposed that appearance of truncated YB-1 in the nucleus may predict multiple drug resistance. Here, we compared functional activities of the full-length and truncated YB-1 proteins and showed that the truncated form was more efficient in protecting cells against doxorubicin treatment. Both forms of YB-1 induced changes in expression of various genes without affecting those responsible for drug resistance. Interestingly, although YB-1 cleavage did not significantly affect its DNA binding properties, truncated YB-1 was detected in complexes with Mre11 and Rad50 under genotoxic stress conditions. We conclude that both full-length and truncated YB-1 are capable of protecting cells against DNA damaging agents, and the truncated form may have an additional function in DNA repair.
Original language | English (US) |
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Pages (from-to) | 3791-3803 |
Number of pages | 13 |
Journal | Cell Cycle |
Volume | 12 |
Issue number | 24 |
DOIs | |
State | Published - Dec 15 2013 |
Externally published | Yes |
Keywords
- Cleavage
- DNA damage
- DNA reparation
- Drug resistance
- Nuclear localization
- PEST
- Proteasome
- Truncation
- YB-1
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology