Activating transcription factor 3 is a member of the mammalian activation transcription factor/cAMP responsive element-binding (CREB) protein family of transcription factors. Multiple transcript variants encoding two different isoforms have been found for this gene. The longer isoform represses rather than activates transcription from promoters with ATF binding elements. The shorter isoform (deltaZip2) lacks the leucine zipper protein-dimerization motif and does not bind to DNA, and it stimulates transcription, it is presumed, by sequestering inhibitory co-factors away from the promoter. It is possible that alternative splicing of the ATF3 gene may be physiologically important in the regulation of target genes.[2]
Clinical significance
ATF-3 is induced upon physiological stress in various tissues.[3] It is also a marker of regeneration following injury of dorsal root ganglion neurons in Pain Research.[4]
↑Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID16169070.
↑Yan C, Wang H, Boyd DD (March 2002). "ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter". J. Biol. Chem. 277 (13): 10804–12. doi:10.1074/jbc.M112069200. PMID11792711.
↑Kang Y, Chen CR, Massagué J (April 2003). "A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells". Mol. Cell. 11 (4): 915–26. doi:10.1016/s1097-2765(03)00109-6. PMID12718878.
Further reading
Hai TW, Liu F, Coukos WJ, Green MR (1990). "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers". Genes Dev. 3 (12B): 2083–90. doi:10.1101/gad.3.12b.2083. PMID2516827.
Hagmeyer BM, Duyndam MC, Angel P, de Groot RP, Verlaan M, Elfferich P, van der Eb A, Zantema A (1996). "Altered AP-1/ATF complexes in adenovirus-E1-transformed cells due to EIA-dependent induction of ATF3". Oncogene. 12 (5): 1025–32. PMID8649793.
Allan AL, Albanese C, Pestell RG, LaMarre J (2001). "Activating transcription factor 3 induces DNA synthesis and expression of cyclin D1 in hepatocytes". J. Biol. Chem. 276 (29): 27272–80. doi:10.1074/jbc.M103196200. PMID11375399.
Zhang C, Kawauchi J, Adachi MT, Hashimoto Y, Oshiro S, Aso T, Kitajima S (2002). "Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is implicated in human vascular endothelial cell death by homocysteine". Biochem. Biophys. Res. Commun. 289 (3): 718–24. doi:10.1006/bbrc.2001.6044. PMID11726207.
Yan C, Wang H, Boyd DD (2002). "ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter". J. Biol. Chem. 277 (13): 10804–12. doi:10.1074/jbc.M112069200. PMID11792711.
Shaheduzzaman S, Krishnan V, Petrovic A, Bittner M, Meltzer P, Trent J, Venkatesan S, Zeichner S (2002). "Effects of HIV-1 Nef on cellular gene expression profiles". J. Biomed. Sci. 9 (1): 82–96. doi:10.1007/BF02256581. PMID11810028.
Kawauchi J, Zhang C, Nobori K, Hashimoto Y, Adachi MT, Noda A, Sunamori M, Kitajima S (2002). "Transcriptional repressor activating transcription factor 3 protects human umbilical vein endothelial cells from tumor necrosis factor-alpha-induced apoptosis through down-regulation of p53 transcription". J. Biol. Chem. 277 (41): 39025–34. doi:10.1074/jbc.M202974200. PMID12161427.
Zhang C, Gao C, Kawauchi J, Hashimoto Y, Tsuchida N, Kitajima S (2002). "Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p53". Biochem. Biophys. Res. Commun. 297 (5): 1302–10. doi:10.1016/S0006-291X(02)02382-3. PMID12372430.
Fan F, Jin S, Amundson SA, Tong T, Fan W, Zhao H, Zhu X, Mazzacurati L, Li X, Petrik KL, Fornace AJ, Rajasekaran B, Zhan Q (2002). "ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growth". Oncogene. 21 (49): 7488–96. doi:10.1038/sj.onc.1205896. PMID12386811.
Nobori K, Ito H, Tamamori-Adachi M, Adachi S, Ono Y, Kawauchi J, Kitajima S, Marumo F, Isobe M (2003). "ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: a novel cardioprotective role of ATF3". J. Mol. Cell. Cardiol. 34 (10): 1387–97. doi:10.1006/jmcc.2002.2091. PMID12392999.
Kang Y, Chen CR, Massagué J (2003). "A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells". Mol. Cell. 11 (4): 915–26. doi:10.1016/S1097-2765(03)00109-6. PMID12718878.
Newman JR, Keating AE (2003). "Comprehensive identification of human bZIP interactions with coiled-coil arrays". Science. 300 (5628): 2097–101. doi:10.1126/science.1084648. PMID12805554.
Kool J, Hamdi M, Cornelissen-Steijger P, van der Eb AJ, Terleth C, van Dam H (2003). "Induction of ATF3 by ionizing radiation is mediated via a signaling pathway that includes ATM, Nibrin1, stress-induced MAPkinases and ATF-2". Oncogene. 22 (27): 4235–42. doi:10.1038/sj.onc.1206611. PMID12833146.
↑Koh EH, Park JY, Park HS, Jeon MJ, Ryu JW, Kim M, Kim SY, Kim MS, Kim SW, Park IS, Youn JH, Lee KU (December 2007). "Essential role of mitochondrial function in adiponectin synthesis in adipocytes". Diabetes. 56 (12): 2973–81. doi:10.2337/db07-0510. PMID17827403.