Y-box factor YB1 controls p53 apoptotic function.
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 have continued to explore YB1/p53 interactions. We report that transcriptionally active p53 is required for nuclear localization of YB1. We go on to show that nuclear YB1 regulates p53 function. Our data demonstrate that YB1 inhibits the ability of p53 to cause cell death and to transactivate cell death genes, but does not interfere with the ability of p53 to transactivate the CDKN1A gene, encoding the kinase p21(WAF1/CIP1) required for cell cycle arrest, nor the MDM2 gene. We also show that nuclear YB1 is associated with a failure to increase the level of the Bax protein in normal mammary epithelial cells after stress activation of p53. Together these data suggest that (nuclear) YB1 selectively alters p53 activity, which may in part provide an explanation for the correlation of nuclear YB1 with drug resistance and poor tumor prognosis.
Homer
Craig
C
Pathology Department, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, Otago 9001, New Zealand.
Knight
Deborah A
DA
Hananeia
Lynne
L
Sheard
Philip
P
Risk
Joanna
J
Lasham
Annette
A
Royds
Janice A
JA
Braithwaite
Antony W
AW
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism; D011401:Promoter Regions, Genetic; D021381:Protein Transport / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000235:genetics
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C486169:Ybx1 protein, rat; D051028:bcl-2-Associated X Protein