Activating transcription factor 3, a stress sensor, activates p53 by blocking its ubiquitination

Chunhong Yan, Dan Lu, Tsonwin Hai, Douglas D. Boyd

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Activating transcription factor 3 (ATF3) is rapidly induced by diverse environmental insults including genotoxic stress. We report herein that its interaction with p53, enhanced by genotoxic stress, stabilizes the tumor suppressor thereby augmenting functions of the latter. Overexpression of ATF3 (but not a mutated ATF3 protein (Δ102-139) devoid of its p53-binding region) prevents p53 from MDM2-mediated degradation and leads to increased transcription from p53-regulated promoters. ATF3, but not the Δ102-139 protein, binds the p53 carboxy-terminus and diminishes its ubiquitination and nuclear export. Genotoxic-stressed ATF3-null mouse embryonic fibroblasts, or cells in which ATF3 was reduced by small interference RNA, show inefficient p53 induction and impaired apoptosis compared with wild-type cells. ATF3-null cells (but not wild-type cells), which poorly accumulate p53, are transformed by oncogenic Ras. Thus, ATF3 is a novel stress-activated regulator of p53 protein stability/ function providing the cell with a means of responding to a wide range of environmental insult, thus maintaining DNA integrity and protecting against cell transformation.

Original languageEnglish (US)
Pages (from-to)2425-2435
Number of pages11
JournalEMBO Journal
Volume24
Issue number13
DOIs
StatePublished - Jul 6 2005

Fingerprint

Activating Transcription Factor 3
Ubiquitination
Sensors
DNA Damage
Null Lymphocytes
Proteins
Cell Nucleus Active Transport
Protein Stability
Transcription
Fibroblasts
RNA Interference
Tumors
RNA
Apoptosis

Keywords

  • ATF3
  • Stability
  • Stress
  • Ubiquitination
  • p53

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Activating transcription factor 3, a stress sensor, activates p53 by blocking its ubiquitination. / Yan, Chunhong; Lu, Dan; Hai, Tsonwin; Boyd, Douglas D.

In: EMBO Journal, Vol. 24, No. 13, 06.07.2005, p. 2425-2435.

Research output: Contribution to journalArticle

Yan, Chunhong ; Lu, Dan ; Hai, Tsonwin ; Boyd, Douglas D. / Activating transcription factor 3, a stress sensor, activates p53 by blocking its ubiquitination. In: EMBO Journal. 2005 ; Vol. 24, No. 13. pp. 2425-2435.
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