Accession Number:

ADA415516

Title:

G1 Cell Cycle Control by Regulated Proteolysis in Normal and Tumorigenic Breast Cells

Descriptive Note:

Annual Summary rept. 1 Sep 2001-31 Aug 2002

Corporate Author:

NORTH CAROLINA UNIV AT CHAPEL HILL

Personal Author(s):

Report Date:

2002-09-01

Pagination or Media Count:

10.0

Abstract:

The p53 gene mediates a major tumor suppression pathway that is frequently altered in human tumors, including breast cancer. The p53 protein presents in low amounts in normally growing cells and is activated in response to physiological insults. MDM2 regulates p53 either through inhibiting p53s transactivating function in the nucleus or by targeting p53 degradation in the cytoplasm. We identified a novel nuclear export signal NES in the NH2-terminus of p53, spanning residues 11 to 27 and containing two serine residues phosphorylated following DNA damage, which was required for p53 nuclear export in collaboration with the COOH-terminal NES. Sersub 15-phosphorylated p53 induced by UV irradiation was not exported. Thus, DNA damage-induced phosphorylation may achieve optimal p53 activation through inhibiting both MDM2 binding to and the nuclear export of p53. We have previously discovered that ARF, a tumor suppressor that is induced by various oncogenic insults and functions to activates p53, blocks p53 degradation by MDM2 via inhibiting p53 nuclear export. Our current finding expands the role of nuclear export in controlling p53.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE