Format

Send to

Choose Destination
Oncogene. 2003 Jan 16;22(2):161-7.

ATM is a target for positive regulation by E2F-1.

Author information

1
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.

Abstract

The E2F-1 transcription factor is a critical downstream target of the tumor suppressor, RB. When activated, E2F-1 induces cell proliferation. In addition, deregulation of E2F-1 constitutes an oncogenic stress that can induce apoptosis. The protein kinase ATM is a pivotal mediator of the response to another type of stress, genotoxic stress. In response to ionizing radiation, ATM activates the tumor suppressor p53, a key player in the control of cell growth and viability. We show here that E2F-1 elevates ATM promoter activity and induces an increase in ATM mRNA and protein levels. This is accompanied by an E2F-induced increase in p53 phosphorylation. Expression of the E7 protein of HPV16, which dissociates RB/E2F complexes, also induces the elevation of ATM levels and p53 phosphorylation, implicating endogenous E2F in these phenomena. These data demonstrate that ATM is transcriptionally regulated by E2F-1 and suggest that ATM serves as a novel, ARF-independent functional link between the RB/E2F pathway and p53.

PMID:
12527885
DOI:
10.1038/sj.onc.1206144
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center