Journal
ONCOGENE
Volume 29, Issue 3, Pages 403-410Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.321
Keywords
YB-1; oncoprotein; proteolysis; nuclear; translocation
Funding
- National Health & Medical Research Council of Australia [423405, 477100]
- Cancer Institute NSW [05/RLP/1-01]
- Health Research Council of New Zealand [07/284A]
- Children's Medical Research Institute Jeans-for-Genes Campaign
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Y-box-binding protein 1 (YB-1) is an oncogenic transcription factor whose overexpression and nuclear localization is associated with tumor progression and drug resistance. Transcriptional activation of YB-1 in response to genotoxic stress is believed to occur in the cytoplasm through sequence-specific endoproteolytic cleavage by the 20S Proteasome, followed by nuclear translocation of cleaved YB-1. To study the proteolysis model, we developed a two-step affinity purification of endogenous YB-1 protein species and characterized the products using mass spectrometry. Whereas full-length YB-1 was readily identified, the smaller protein band thought to be activated YB-1 was identified as hnRNP A1. An antibody specific for YB-1 was generated, which revealed only one YB-1 species, even after genotoxic stress-induced nuclear YB-1 translocation. These findings warrant re-evaluation of the mechanism of YB-1 nuclear translocation and transcriptional activation. The relationship between nuclear YB-1 and tumor progression may also have to re-evaluated in some cases. Oncogene (2010) 29, 403-410; doi:10.1038/onc.2009.321; published online 19 October 2009
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