This gene encodes atranscription factor that is a member of theleucine zipper family of DNA-binding proteins. This protein binds to thecAMP-responsive element (CRE), an octameric palindrome. The protein forms a homodimer or heterodimer withc-Jun. The protein is also ahistone 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 onchromatin components. Additional transcript variants have been identified but their biological validity has not been determined.[5]
The gene atf2 is located at human chromosome 2q32.[6] 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.[7] ATF-2 is normally activated in response to signals that converge onstress-activated protein kinases p38 andJNK.[8] ATF-2 phosphorylation in response to treatment of cells with tumor promoterphorbol ester has been demonstrated.[9]
Several studies implicate abnormal activation of ATF-2 in growth and progression of mammalian skin tumors.[10][11] ATF-2 may mediate oncogenesis caused by mutantRas protein[12] and regulate maintenance of the aggressive cancer phenotype of some types of epithelial cells.
ATF2 has also been shown to bephosphorylated at itsC-terminal (serine 472 and 480 in mouse; serine 490 and 498 in human) byATM upondouble-stranded breaks.[13] Mice with mutations of these two serines are sensitive to irradiation and easier to tumorigenesis under p53 knockout background.
^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.PMID1833307.
^Papassava P, Gorgoulis VG, Papaevangeliou D, Vlahopoulos S, van Dam H, Zoumpourlis V (2004). "Overexpression of activating transcription factor-2 is required for tumor growth and progression in mouse skin tumors".Cancer Res.64 (23):8573–84.doi:10.1158/0008-5472.CAN-03-0955.PMID15574764.S2CID14845890.
^Vlahopoulos SA, Logotheti S, Mikas D, Giarika A, Gorgoulis V, Zoumpourlis V (17 March 2008). "The role of ATF-2 in oncogenesis".BioEssays.30 (4):314–27.doi:10.1002/bies.20734.PMID18348191.S2CID678541.
^Newell CL, Deisseroth AB, Lopez-Berestein G (July 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.doi:10.1002/jlb.56.1.27.PMID8027667.S2CID85570533.
^Murata T, Shinozuka Y, Obata Y, Yokoyama KK (May 2008). "Phosphorylation of two eukaryotic transcription factors, Jun dimerization protein 2 and activation transcription factor 2, in Escherichia coli by Jun N-terminal kinase 1".Anal. Biochem.376 (1):115–21.doi:10.1016/j.ab.2008.01.038.PMID18307971.
Denys H, Desmet R, Stragier M, Vergison R, Lemahieu SF (1977). "Cystitis emphysematosa".Acta Urol Belg.45 (4):327–31.PMID602896.
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.Bibcode:1992Natur.358..331K.doi:10.1038/358331a0.PMID1641004.S2CID9770957.
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.PMID1833307.
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.PMID1838349.
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.doi:10.1002/jlb.56.1.27.PMID8027667.S2CID85570533.
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.Bibcode:1997BBRC..235..533K.doi:10.1006/bbrc.1997.6849.PMID9207191.
