ATM is a target for positive regulation by E2F-1

Oncogene. 2003 Jan 16;22(2):161-7. doi: 10.1038/sj.onc.1206144.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / cytology
  • Animals
  • Apoptosis / physiology
  • Ataxia Telangiectasia Mutated Proteins
  • Binding Sites
  • Caffeine / pharmacology
  • Cell Cycle Proteins*
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Gene Expression Regulation
  • Humans
  • Mice
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism
  • Papillomavirus E7 Proteins
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Transcription Factor DP1
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, mouse
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Receptors, Estrogen
  • Recombinant Proteins
  • Transcription Factor DP1
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • Caffeine
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Atm protein, mouse
  • Protein-Serine-Threonine Kinases