Accession Number:

ADA433416

Title:

Analysis of the ARF/p53 Pathway During Oncogenic Stimulation

Descriptive Note:

Annual summary 1 Jul 2003-30 Jun 2004

Corporate Author:

COLD SPRING HARBOR LAB NY

Personal Author(s):

Report Date:

2004-07-01

Pagination or Media Count:

12.0

Abstract:

The purpose of this study was to identify and study new targets involved in oncogene-induced apoptosis. The research was centered on microarray studies that used the adenovirus ElA oncoprotein to probe the relationship between proliferation and apoptosis in human cells. During the course of the first year of studies, Mad2, the mitotic checkpoint gene, was identified as a gene upregulated by ElA on microarrays. During the past year, we have gone on to show that Mad2 was a direct target of E2F and that disruption of the Rb pathway and deregulation of E2F produced aberrantly high levels of Mad2, which are mis-expressed throughout the cell cycle. Thus, E2F couples cell cycle progression to both apoptosis and mitotic control. We have gone on to show that elevated Mad2 is both necessary and sufficient to produce the genomic instability and aneuploidy observed in Rb deficient cells. These results are currently accepted for publication in Nature. Note Zaher Nanle graduated in May of 2003 and has taken a position at Washington University. None of the new experiments described in this report were carried out using this funding. However, since the studies were initiated under this fellowship, we have chosen to report them here.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE