Activating transcription factor 2

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External IDs	GeneCards: [1]
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Species	Human	Mouse
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RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
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Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.

Function

This gene encodes a transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein binds to the cAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer with c-Jun and stimulates CRE-dependent transcription. The protein 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. Additional transcript variants have been identified but their biological validity has not been determined.

The gene atf2 is located at human chromosome 2q32. The protein ATF-2 has 505 amino acids. Studies in mice indicate a role for ATF-2 in the development of nervous system and the skeleton. ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38 and JNK. ATF-2 phosphorylation in response to treatment of cells with tumor promoter phorbol ester has been demonstrated.

Several studies implicate abnormal activation of ATF-2 in growth and progression of mammalian skin tumors. ATF-2 may mediate oncogenesis caused by mutant Ras protein and regulate maintenance of the aggressive cancer phenotype of some types of epithelial cells. ATF2 has also been shown to be phosphorylated at its C-terminal (Serine 472 and 480 in mouse; Serine 490 and 498 in human) by ATM upon double-stranded breaks. Mice with mutations of these two serines are sensitive to irradiation and easier to tumorigenesis under p53 knockout background.

ATF2 has also been shown to be phosphorylated at its C-terminal (serine 472 and 480 in mouse; serine 490 and 498 in human) by ATM upon double-stranded breaks.

Interactions

Activating transcription factor 2 has been shown to interact with

• C-jun,
• Casein kinase 2, alpha 1,
• CREB binding protein,
• CSNK2A2,
• JDP2,
• MAPK14,
• MAPK8,
• Mothers against decapentaplegic homolog 3
• NCOA6,
• RUVBL2,
• UBE2I.

See also

• Activating transcription factor

External links

• Human ATF2 genome location and ATF2 gene details page in the UCSC Genome Browser.

Further reading

• Denys H, Desmet R, Stragier M, Vergison R, Lemahieu SF (1977). "Cystitis emphysematosa". Acta Urol Belg. 45 (4): 327–31. PMID 602896.
• Kim SJ, Wagner S, Liu F, O'Reilly MA, Robbins PD, Green MR (1992). "Retinoblastoma gene product activates expression of the human TGF-beta 2 gene through transcription factor ATF-2". Nature. 358 (6384): 331–4. doi:10.1038/358331a0. PMID 1641004.
• Hai T, Curran T (1991). "Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3720–4. doi:10.1073/pnas.88.9.3720. PMC 51524. PMID 1827203.
• Hoeffler JP, Lustbader JW, Chen CY (1991). "Identification of multiple nuclear factors that interact with cyclic adenosine 3',5'-monophosphate response element-binding protein and activating transcription factor-2 by protein-protein interactions". Mol. Endocrinol. 5 (2): 256–66. doi:10.1210/mend-5-2-256. PMID 1828107.
• Ozawa K, Sudo T, Soeda E, Yoshida MC, Ishii S (1991). "Assignment of the human CREB2 (CRE-BP1) gene to 2q32". Genomics. 10 (4): 1103–4. doi:10.1016/0888-7543(91)90210-6. PMID 1833307.
• Diep A, Li C, Klisak I, Mohandas T, Sparkes RS, Gaynor R, Lusis AJ (1991). "Assignment of the gene for cyclic AMP-response element binding protein 2 (CREB2) to human chromosome 2q24.1-q32". Genomics. 11 (4): 1161–3. doi:10.1016/0888-7543(91)90047-I. PMID 1838349.
• Kara CJ, Liou HC, Ivashkiv LB, Glimcher LH (1990). "A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain". Mol. Cell. Biol. 10 (4): 1347–57. PMC 362236. PMID 2320002.
• Gonzalez GA, Yamamoto KK, Fischer WH, Karr D, Menzel P, Biggs W, Vale WW, Montminy MR (1989). "A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence". Nature. 337 (6209): 749–52. doi:10.1038/337749a0. PMID 2521922.
• Maekawa T, Sakura H, Kanei-Ishii C, Sudo T, Yoshimura T, Fujisawa J, Yoshida M, Ishii S (1989). "Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain". EMBO J. 8 (7): 2023–8. PMC 401081. PMID 2529117.
• Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (1995). "Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine". J. Biol. Chem. 270 (13): 7420–6. doi:10.1074/jbc.270.13.7420. PMID 7535770.
• Livingstone C, Patel G, Jones N (1995). "ATF-2 contains a phosphorylation-dependent transcriptional activation domain". EMBO J. 14 (8): 1785–97. PMC 398272. PMID 7737129.
• van Dam H, Wilhelm D, Herr I, Steffen A, Herrlich P, Angel P (1995). "ATF-2 is preferentially activated by stress-activated protein kinases to mediate c-jun induction in response to genotoxic agents". EMBO J. 14 (8): 1798–811. PMC 398273. PMID 7737130.
• Zhou Q, Gedrich RW, Engel DA (1995). "Transcriptional repression of the c-fos gene by YY1 is mediated by a direct interaction with ATF/CREB". J. Virol. 69 (7): 4323–30. PMC 189172. PMID 7769693.
• Newell CL, Deisseroth AB, Lopez-Berestein G (1994). "Interaction of nuclear proteins with an AP-1/CRE-like promoter sequence in the human TNF-alpha gene". J. Leukoc. Biol. 56 (1): 27–35. PMID 8027667.
• Nomura N, Zu YL, Maekawa T, Tabata S, Akiyama T, Ishii S (1993). "Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1". J. Biol. Chem. 268 (6): 4259–66. PMID 8440710.
• Martin ML, Lieberman PM, Curran T (1996). "Fos-Jun dimerization promotes interaction of the basic region with TFIIE-34 and TFIIF". Mol. Cell. Biol. 16 (5): 2110–8. PMC 231198. PMID 8628277.
• Yang L, Lanier ER, Kraig E (1997). "Identification of a novel, spliced variant of CREB that is preferentially expressed in the thymus". J. Immunol. 158 (6): 2522–5. PMID 9058782.
• Shuman JD, Cheong J, Coligan JE (1997). "ATF-2 and C/EBPalpha can form a heterodimeric DNA binding complex in vitro. Functional implications for transcriptional regulation". J. Biol. Chem. 272 (19): 12793–800. doi:10.1074/jbc.272.19.12793. PMID 9139739.
• Fukunaga R, Hunter T (1997). "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates". EMBO J. 16 (8): 1921–33. doi:10.1093/emboj/16.8.1921. PMC 1169795. PMID 9155018.
• Kumar S, McDonnell PC, Gum RJ, Hand AT, Lee JC, Young PR (1997). "Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles". Biochem. Biophys. Res. Commun. 235 (3): 533–8. doi:10.1006/bbrc.1997.6849. PMID 9207191.