Accession Number:

ADA394773

Title:

Regulation of the Tumor Suppressor Activity of p53 in Human Breast Cancer

Descriptive Note:

Final rept. 1 Aug 1997-1 Aug 2000

Corporate Author:

MOUNT SINAI SCHOOL OF MEDICINE NEW YORK

Personal Author(s):

Report Date:

2000-09-01

Pagination or Media Count:

92.0

Abstract:

Consistent with its function as a transcription factor, the ability to bind to DNA is central to the tumor suppressor activity of p53. Genetic alteration of p53 resulting in loss-of-function is a common event in human cancer. To identify novel mechanisms in human breast cancer involving functional inactivation of wild-type p53 besides such direct genetic alteration, cellular factors that regulate the ability of p53 to bind to DNA were identified and characterized. The high mobility group proteins HMG-1, HMG-2, and HMG-I all enhanced the sequence-specific binding of p53 to DNA in vitro, but only HMG-1 stimulated the transcriptional activity of p53 in cells. The transcriptional activator Sp1 bound in a sequence-specific manner to a distinct subset of p53 response elements, but, in contrast to p53, the binding of Sp1 to DNA was inhibited by HMG-1. An intact Sp1 binding site was shown to be required for efficient p53-dependent activation of the bar promoter. It is proposed that alterations in the interaction of HMG-1 and Sp1 with p53 may contribute to functional inactivation of p53 in human breast tumors.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE