Activating transcription factor 2

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Protein ATF2 PDB 1bhi.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesATF2, CRE-BP1, CREB-2, CREB2, HB16, TREB7, activating transcription factor 2
External IDsOMIM: 123811 MGI: 109349 HomoloGene: 31061 GeneCards: ATF2
Gene location (Human)
Chromosome 2 (human)
Chr.Chromosome 2 (human)[1]
Chromosome 2 (human)
Genomic location for ATF2
Genomic location for ATF2
Band2q31.1Start175,072,250 bp[1]
End175,168,382 bp[1]
RNA expression pattern
PBB GE ATF2 212984 at fs.png

PBB GE ATF2 205446 s at fs.png
More reference expression data
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 2: 175.07 – 175.17 MbChr 2: 73.82 – 73.89 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.[5]


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.[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 on stress-activated protein kinases p38 and JNK.[8] ATF-2 phosphorylation in response to treatment of cells with tumor promoter phorbol 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 mutant Ras protein[12] 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.[13] Mice with mutations of these two serines are sensitive to irradiation and easier to tumorigenesis under p53 knockout background.


Activating transcription factor 2 has been shown to interact with

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115966 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027104 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: ATF2 activating transcription factor 2".
  6. ^ 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.
  7. ^ Reimold AM, Grusby MJ, Kosaras B, Fries JW, Mori R, Maniwa S, Clauss IM, Collins T, Sidman RL, Glimcher MJ, Glimcher LH (1996). "Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice". Nature. 379 (6562): 262–5. doi:10.1038/379262a0. PMID 8538792.
  8. ^ Gupta S, Campbell D, Dérijard B, Davis RJ (1995). "Transcription factor ATF2 regulation by the JNK signal transduction pathway". Science. 267 (5196): 389–93. doi:10.1126/science.7824938. PMID 7824938.
  9. ^ Yamasaki T, Takahashi A, Pan J, Yamaguchi N, Yokoyama KK (March 2009). "Phosphorylation of Activation Transcription Factor-2 at Serine 121 by Protein Kinase C Controls c-Jun-mediated Activation of Transcription". J. Biol. Chem. 284 (13): 8567–81. doi:10.1074/jbc.M808719200. PMC 2659215. PMID 19176525.
  10. ^ Leslie MC, Bar-Eli M (2005). "Regulation of gene expression in melanoma: new approaches for treatment". J. Cell. Biochem. 94 (1): 25–38. doi:10.1002/jcb.20296. PMID 15523674.
  11. ^ 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. PMID 15574764.
  12. ^ 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. PMID 18348191.
  13. ^ Bhoumik A, Takahashi S, Breitweiser W, Shiloh Y, Jones N, Ronai Z (May 2005). "ATM-dependent phosphorylation of ATF2 is required for the DNA damage response". Mol. Cell. 18 (5): 577–87. doi:10.1016/j.molcel.2005.04.015. PMC 2954254. PMID 15916964.
  14. ^ 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. PMID 8027667.
  15. ^ Kara CJ, Liou HC, Ivashkiv LB, Glimcher LH (April 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. doi:10.1128/MCB.10.4.1347. PMC 362236. PMID 2320002.
  16. ^ Hai T, Curran T (May 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.
  17. ^ a b Yamaguchi Y, Wada T, Suzuki F, Takagi T, Hasegawa J, Handa H (August 1998). "Casein kinase II interacts with the bZIP domains of several transcription factors". Nucleic Acids Res. 26 (16): 3854–61. doi:10.1093/nar/26.16.3854. PMC 147779. PMID 9685505.
  18. ^ Sano Y, Tokitou F, Dai P, Maekawa T, Yamamoto T, Ishii S (October 1998). "CBP alleviates the intramolecular inhibition of ATF-2 function". J. Biol. Chem. 273 (44): 29098–105. doi:10.1074/jbc.273.44.29098. PMID 9786917.
  19. ^ 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. PMID 18307971.
  20. ^ a b Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (March 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.
  21. ^ a b Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.
  22. ^ a b Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7337–42. doi:10.1073/pnas.94.14.7337. PMC 23822. PMID 9207092.
  23. ^ Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z (December 1997). "c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors". J. Biol. Chem. 272 (51): 32163–8. doi:10.1074/jbc.272.51.32163. PMID 9405416.
  24. ^ Sano Y, Harada J, Tashiro S, Gotoh-Mandeville R, Maekawa T, Ishii S (March 1999). "ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-beta signaling". J. Biol. Chem. 274 (13): 8949–57. doi:10.1074/jbc.274.13.8949. PMID 10085140.
  25. ^ Hong S, Choi HM, Park MJ, Kim YH, Choi YH, Kim HH, Choi YH, Cheong J (April 2004). "Activation and interaction of ATF2 with the coactivator ASC-2 are responsive for granulocytic differentiation by retinoic acid". J. Biol. Chem. 279 (17): 16996–7003. doi:10.1074/jbc.M311752200. PMID 14734562.
  26. ^ Cho SG, Bhoumik A, Broday L, Ivanov V, Rosenstein B, Ronai Z (December 2001). "TIP49b, a regulator of activating transcription factor 2 response to stress and DNA damage". Mol. Cell. Biol. 21 (24): 8398–413. doi:10.1128/MCB.21.24.8398-8413.2001. PMC 100004. PMID 11713276.
  27. ^ Firestein R, Feuerstein N (March 1998). "Association of activating transcription factor 2 (ATF2) with the ubiquitin-conjugating enzyme hUBC9. Implication of the ubiquitin/proteasome pathway in regulation of ATF2 in T cells". J. Biol. Chem. 273 (10): 5892–902. doi:10.1074/jbc.273.10.5892. PMID 9488727.

External links[edit]

Further reading[edit]

External links[edit]

  • PDBe-KB provides an overview of all the structure information available in the PDB for Human Cyclic AMP-dependent transcription factor ATF-2