The stress-responsive gene ATF3 mediates dichotomous UV responses by regulating the Tip60 and p53 proteins

Hongmei Cui, Xingyao Li, Chunhua Han, Qi En Wang, Hongbo Wang, Hanfei Ding, Junran Zhang, Chunhong Yan

Research output: Contribution to journalArticle

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Abstract

The response toUVirradiation is important for a cell to maintain its genetic integrity when challenged by environmental genotoxins. An immediate early response to UV irradiation is the rapid induction of activating transcription factor 3 (ATF3) expression. Although emerging evidence has linked ATF3 to stress pathways regulated by the tumor suppressor p53 and the histone acetyltransferase Tip60, the role of ATF3 in the UV response remains largely unclear. Here, we report that ATF3 mediated dichotomous UV responses. Although UV irradiation enhanced the binding of ATF3 to Tip60, knockdown of ATF3 expression decreased Tip60 stability, thereby impairing Tip60 induction by UV irradiation. In line with the role of Tip60 in mediating UV-induced apoptosis, ATF3 promoted the death of p53-defective cells in response to UV irradiation. However, ATF3 could also activate p53 and promote p53-mediated DNA repair, mainly through altering histone modifications that could facilitate recruitment of DNA repair proteins (such as DDB2) to damaged DNA sites. As a result, ATF3 rather protected the p53 wild-type cells from UV-induced apoptosis. Our results thus indicate that ATF3 regulates cell fates upon UV irradiation in a p53-dependent manner.

Original languageEnglish (US)
Pages (from-to)10847-10857
Number of pages11
JournalJournal of Biological Chemistry
Volume291
Issue number20
DOIs
StatePublished - May 13 2016

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Activating Transcription Factor 3
Genes
Proteins
Irradiation
DNA Repair
DNA
Repair
Histone Code
Apoptosis
Histone Acetyltransferases
Mutagens
Histones
Tumors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The stress-responsive gene ATF3 mediates dichotomous UV responses by regulating the Tip60 and p53 proteins. / Cui, Hongmei; Li, Xingyao; Han, Chunhua; Wang, Qi En; Wang, Hongbo; Ding, Hanfei; Zhang, Junran; Yan, Chunhong.

In: Journal of Biological Chemistry, Vol. 291, No. 20, 13.05.2016, p. 10847-10857.

Research output: Contribution to journalArticle

Cui, Hongmei ; Li, Xingyao ; Han, Chunhua ; Wang, Qi En ; Wang, Hongbo ; Ding, Hanfei ; Zhang, Junran ; Yan, Chunhong. / The stress-responsive gene ATF3 mediates dichotomous UV responses by regulating the Tip60 and p53 proteins. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 20. pp. 10847-10857.
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