BACKGROUND Activating Transcription Factor 2 (ATF2) is a member of the bZIP family of transcription factors. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. It is activated upon its phosphorylation by stress-activated kinases in response to stress and cytokine stimuli.1 JNK and p38MAPK phosphorylated ATF2 on Thr69 and Thr71 and activated ATF2.2 Transcriptional activity of ATF2 depends on its heterodimerization with members of the AP1 family, including c-Jun3 or interaction with viral proteins, including v-Jun, E1A, and the Tax proteins. ATF2 forms a homodimer or heterodimer with c-Jun and stimulates CRE-dependent transcription. It is also a histone acetyltransferase (HAT) that specifically acetylates histones H2B and H4 in vitro; thus it may represent a class of sequence-specific factors that activate transcription by direct effects on chromatin components. ATF2 target genes include AP1-responsive genes, such as cyclin A, IFN-beta, and TNF-alpha. Intriguingly, ATF2 has also been implicated in the DNA damage response, through its phosphorylation by phosphoinositide-3-kinase-related protein kinase, including ATM.4 This phosphorylation is required for intra-S phase checkpoint control and for its colocalization with components of the Mre11–Rad50–Nbs1 (MRN) complex within DNA damage repair foci.
REFERENCES
1. van Dam, H. et al: EMBO J. 14:1798-1811, 1995
2. Gupta, S. et al: Sciences 267:389-393, 1995
3. Bhoumik, A. et al: Proc. Natl. Acad. Sci. USA 105:1674-9, 2008
4. Benbrook, D.M. & Jones, N.C.: Oncogene 5:295-302, 1990
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