Biology:Activating transcription factor 2
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Short description: Protein-coding gene in the species Homo sapiens
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Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.[1]
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. 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.[1]
The gene atf2 is located at human chromosome 2q32.[2] 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.[3] ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38 and JNK.[4] ATF-2 phosphorylation in response to treatment of cells with tumor promoter phorbol ester has been demonstrated.[5]
Several studies implicate abnormal activation of ATF-2 in growth and progression of mammalian skin tumors.[6][7] ATF-2 may mediate oncogenesis caused by mutant Ras protein[8] 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.[9] Mice with mutations of these two serines are sensitive to irradiation and easier to tumorigenesis under p53 knockout background.
Interactions
Activating transcription factor 2 has been shown to interact with
- C-jun,[10][11][12]
- Casein kinase 2, alpha 1,[13]
- CREB binding protein,[14]
- CSNK2A2,[13]
- JDP2,[15]
- MAPK14,[16][17][18]
- MAPK8,[16][17][18][19]
- Mothers against decapentaplegic homolog 3[20]
- NCOA6,[21]
- RUVBL2,[22]
- UBE2I.[23]
See also
References
- ↑ 1.0 1.1 "Entrez Gene: ATF2 activating transcription factor 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1386.
- ↑ "Assignment of the human CREB2 (CRE-BP1) gene to 2q32". Genomics 10 (4): 1103–4. 1991. doi:10.1016/0888-7543(91)90210-6. PMID 1833307.
- ↑ "Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice". Nature 379 (6562): 262–5. 1996. doi:10.1038/379262a0. PMID 8538792. Bibcode: 1996Natur.379..262R.
- ↑ "Transcription factor ATF2 regulation by the JNK signal transduction pathway". Science 267 (5196): 389–93. 1995. doi:10.1126/science.7824938. PMID 7824938. Bibcode: 1995Sci...267..389G.
- ↑ "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. March 2009. doi:10.1074/jbc.M808719200. PMID 19176525.
- ↑ "Regulation of gene expression in melanoma: new approaches for treatment". J. Cell. Biochem. 94 (1): 25–38. 2005. doi:10.1002/jcb.20296. PMID 15523674.
- ↑ "Overexpression of activating transcription factor-2 is required for tumor growth and progression in mouse skin tumors". Cancer Res. 64 (23): 8573–84. 2004. doi:10.1158/0008-5472.CAN-03-0955. PMID 15574764.
- ↑ "The role of ATF-2 in oncogenesis". BioEssays 30 (4): 314–27. 17 March 2008. doi:10.1002/bies.20734. PMID 18348191.
- ↑ "ATM-dependent phosphorylation of ATF2 is required for the DNA damage response". Mol. Cell 18 (5): 577–87. May 2005. doi:10.1016/j.molcel.2005.04.015. PMID 15916964.
- ↑ "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. July 1994. doi:10.1002/jlb.56.1.27. PMID 8027667.
- ↑ "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. April 1990. doi:10.1128/MCB.10.4.1347. PMID 2320002.
- ↑ "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. May 1991. doi:10.1073/pnas.88.9.3720. PMID 1827203. Bibcode: 1991PNAS...88.3720H.
- ↑ 13.0 13.1 "Casein kinase II interacts with the bZIP domains of several transcription factors". Nucleic Acids Res. 26 (16): 3854–61. August 1998. doi:10.1093/nar/26.16.3854. PMID 9685505.
- ↑ "CBP alleviates the intramolecular inhibition of ATF-2 function". J. Biol. Chem. 273 (44): 29098–105. October 1998. doi:10.1074/jbc.273.44.29098. PMID 9786917.
- ↑ "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. May 2008. doi:10.1016/j.ab.2008.01.038. PMID 18307971.
- ↑ 16.0 16.1 "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. March 1995. doi:10.1074/jbc.270.13.7420. PMID 7535770.
- ↑ 17.0 17.1 "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. May 2001. doi:10.1074/jbc.M100681200. PMID 11279118.
- ↑ 18.0 18.1 "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. July 1997. doi:10.1073/pnas.94.14.7337. PMID 9207092. Bibcode: 1997PNAS...94.7337T.
- ↑ "c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors". J. Biol. Chem. 272 (51): 32163–8. December 1997. doi:10.1074/jbc.272.51.32163. PMID 9405416.
- ↑ "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. March 1999. doi:10.1074/jbc.274.13.8949. PMID 10085140.
- ↑ "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. April 2004. doi:10.1074/jbc.M311752200. PMID 14734562.
- ↑ "TIP49b, a regulator of activating transcription factor 2 response to stress and DNA damage". Mol. Cell. Biol. 21 (24): 8398–413. December 2001. doi:10.1128/MCB.21.24.8398-8413.2001. PMID 11713276.
- ↑ "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. March 1998. doi:10.1074/jbc.273.10.5892. PMID 9488727.
External links
- Human ATF2 genome location and ATF2 gene details page in the UCSC Genome Browser.
Further reading
- "Cystitis emphysematosa". Acta Urol Belg 45 (4): 327–31. 1977. PMID 602896.
- "Retinoblastoma gene product activates expression of the human TGF-beta 2 gene through transcription factor ATF-2". Nature 358 (6384): 331–4. 1992. doi:10.1038/358331a0. PMID 1641004. Bibcode: 1992Natur.358..331K.
- "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. 1991. doi:10.1073/pnas.88.9.3720. PMID 1827203. Bibcode: 1991PNAS...88.3720H.
- "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. 1991. doi:10.1210/mend-5-2-256. PMID 1828107.
- "Assignment of the human CREB2 (CRE-BP1) gene to 2q32". Genomics 10 (4): 1103–4. 1991. doi:10.1016/0888-7543(91)90210-6. PMID 1833307.
- "Assignment of the gene for cyclic AMP-response element binding protein 2 (CREB2) to human chromosome 2q24.1-q32". Genomics 11 (4): 1161–3. 1991. doi:10.1016/0888-7543(91)90047-I. PMID 1838349.
- "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. 1990. doi:10.1128/MCB.10.4.1347. PMID 2320002.
- "A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence". Nature 337 (6209): 749–52. 1989. doi:10.1038/337749a0. PMID 2521922. Bibcode: 1989Natur.337..749G.
- "Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain". EMBO J. 8 (7): 2023–8. 1989. doi:10.1002/j.1460-2075.1989.tb03610.x. PMID 2529117.
- "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. 1995. doi:10.1074/jbc.270.13.7420. PMID 7535770.
- "ATF-2 contains a phosphorylation-dependent transcriptional activation domain". EMBO J. 14 (8): 1785–97. 1995. doi:10.1002/j.1460-2075.1995.tb07167.x. PMID 7737129.
- "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. 1995. doi:10.1002/j.1460-2075.1995.tb07168.x. PMID 7737130.
- "Transcriptional repression of the c-fos gene by YY1 is mediated by a direct interaction with ATF/CREB". J. Virol. 69 (7): 4323–30. 1995. doi:10.1128/JVI.69.7.4323-4330.1995. PMID 7769693.
- "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. 1994. doi:10.1002/jlb.56.1.27. PMID 8027667.
- "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. 1993. doi:10.1016/S0021-9258(18)53604-8. PMID 8440710.
- "Fos-Jun dimerization promotes interaction of the basic region with TFIIE-34 and TFIIF". Mol. Cell. Biol. 16 (5): 2110–8. 1996. doi:10.1128/mcb.16.5.2110. PMID 8628277.
- "Identification of a novel, spliced variant of CREB that is preferentially expressed in the thymus". J. Immunol. 158 (6): 2522–5. 1997. doi:10.4049/jimmunol.158.6.2522. PMID 9058782.
- "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. 1997. doi:10.1074/jbc.272.19.12793. PMID 9139739.
- "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. 1997. doi:10.1093/emboj/16.8.1921. PMID 9155018.
- "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. 1997. doi:10.1006/bbrc.1997.6849. PMID 9207191.
External links
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Cyclic AMP-dependent transcription factor ATF-2
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