Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor protein p53.
The tumor suppressor protein p53 exerts its cell cycle-regulatory effects through its ability to function as a sequence-specific DNA-binding transcription factor. Herein, we show that p53 physically interacts with specific subregions of steroid receptor coactivator-1 (SRC-1) and its family members, p/CIP (p300/CBP interacting protein), xSRC-3, and AIB1 (amplified in breast cancer), originally isolated as transcription coactivators of nuclear receptors, as demonstrated by the yeast and mammalian two-hybrid tests as well as glutathione S-transferase pull-down assays. Interestingly, cotransfection of HeLa cells with SRC-1- or p/CIP expression vector potentiated the p53-mediated transactivation, whereas AIB1 and xSRC-3 were repressive. All of these SRC-1 members, however, similarly stimulated transactivation mediated by nuclear receptors and AP-1, as previously described. These results suggest that SRC-1 and its family members may differentially modulate the p53 transactivation in vivo.
Lee
S K
SK
Department of Biology, Chonnam National University, Kwangju, Korea.
Kim
H J
HJ
Kim
J W
JW
Lee
J W
JW
D000123:Acetyltransferases; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000099160:LexA Repressor Protein
D000123:Acetyltransferases; D001426:Bacterial Proteins; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000099160:LexA Repressor Protein; C538859:NCOA1 protein, human; C538866:NCOA3 protein, human