The Y-box-binding protein, YB1, is a potential negative regulator of the p53 tumor suppressor.
The p53 tumor suppressor plays a major role in preventing tumor development by transactivating genes to remove or repair potentially tumorigenic cells. Here we show that the Y-box-binding protein, YB1, acts as a negative regulator of p53. Using reporter assays we show that YB1 represses transcription of the p53 promoter in a sequence-specific manner. We also show that YB1 reduces endogenous levels of p53, which in turn reduces p53 activity. Conversely, inhibiting YB1 in a variety of tumor cell lines induces p53 activity, resulting in significant apoptosis via a p53-dependent pathway. These data suggest that YB1 may, in some situations, protect cells from p53-mediated apoptosis, indicating that YB1 may be a good target for the development of new therapeutics.
Lasham
Annette
A
Genesis Research and Development Corporation Limited, P. O. Box 50, Auckland 1001, New Zealand.
Moloney
Stephanie
S
Hale
Tracy
T
Homer
Craig
C
Zhang
You Fang
YF
Murison
J Greg
JG
Braithwaite
Antony W
AW
Watson
James
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C486169:Ybx1 protein, rat