Nuclear localization of Y-box factor YB1 requires wild-type p53.
Nuclear localization and high levels of the Y-box binding protein YB1 appear to be important indicators of drug resistance and tumor prognosis. YB1 also interacts with the p53 tumor suppressor protein. In this paper, we explore a role for p53 in the nuclear localization of YB1. We report that various genotoxic stresses induce nuclear localization of YB1 in a small proportion of treated cells, but only in cells with wild-type p53. We go on to show directly that functional p53 is required for YB1 to translocate to the nucleus. Tumor-associated p53 mutants however are attenuated for YB1 nuclear localization as are mutants mutated in the proline-rich domain of p53. These data link the DNA-damage response of p53 to YB1 nuclear translocation. In addition, we find that YB1 inhibits p53-induced cell death and its ability to trans-activate promoters of genes involved in cell death signaling. Together these data suggest that some forms of p53 cause YB1 to accumulate in the nucleus, which in turn inhibits p53 activity. These results provide a possible explanation for the correlation of nuclear YB1 with drug resistance and poor prognosis in some tumor types, and for the first time implicate p53 in the process of nuclear translocation.
Pathology Department, Dunedin School of Medicine, University of Otago, Box 913, Dunedin, New Zealand.
You Fang
YF
Zhang
Craig
C
Homer
Sara J
SJ
Edwards
Lynne
L
Hananeia
Annette
A
Lasham
Janice
J
Royds
Philip
P
Sheard
Antony W
AW
Braithwaite
D021581:Active Transport, Cell Nucleus; D000260:Adenoviruses, Human; D000970:Antineoplastic Agents / Q000494:pharmacology; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002472:Cell Transformation, Viral; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007700:Kinetics; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1
D000970:Antineoplastic Agents; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D002945:Cisplatin