Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor protein p53

Mol Endocrinol. 1999 Nov;13(11):1924-33. doi: 10.1210/mend.13.11.0365.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • HeLa Cells / metabolism
  • Histone Acetyltransferases
  • Humans
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 3
  • Oncogene Proteins
  • Protein Isoforms
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Transfection
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Bacterial Proteins
  • LexA protein, Bacteria
  • Oncogene Proteins
  • Protein Isoforms
  • Recombinant Proteins
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Acetyltransferases
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • NCOA3 protein, human
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 3
  • Serine Endopeptidases