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词条 Activating transcription factor 2
释义

  1. Function

  2. Interactions

  3. See also

  4. References

  5. External links

  6. Further reading

{{Use dmy dates|date=June 2013}}{{Infobox_gene}}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 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.[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,[14]
  • CREB binding protein,[13]
  • CSNK2A2,[14]
  • 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

  • Activating transcription factor

References

1. ^1 {{Cite web| title = Entrez Gene: ATF2 activating transcription factor 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1386| accessdate = }}
2. ^{{cite journal | vauthors = Ozawa K, Sudo T, Soeda E, Yoshida MC, Ishii S | title = Assignment of the human CREB2 (CRE-BP1) gene to 2q32 | journal = Genomics | volume = 10 | issue = 4 | pages = 1103–4 | year = 1991 | pmid = 1833307 | doi = 10.1016/0888-7543(91)90210-6 }}
3. ^{{cite journal | vauthors = Reimold AM, Grusby MJ, Kosaras B, Fries JW, Mori R, Maniwa S, Clauss IM, Collins T, Sidman RL, Glimcher MJ, Glimcher LH | title = Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice | journal = Nature | volume = 379 | issue = 6562 | pages = 262–5 | year = 1996 | pmid = 8538792 | doi = 10.1038/379262a0 }}
4. ^{{cite journal | vauthors = Gupta S, Campbell D, Dérijard B, Davis RJ | title = Transcription factor ATF2 regulation by the JNK signal transduction pathway | journal = Science | volume = 267 | issue = 5196 | pages = 389–93 | year = 1995 | pmid = 7824938 | doi = 10.1126/science.7824938 }}
5. ^{{cite journal | vauthors = Yamasaki T, Takahashi A, Pan J, Yamaguchi N, Yokoyama KK | title = Phosphorylation of Activation Transcription Factor-2 at Serine 121 by Protein Kinase C Controls c-Jun-mediated Activation of Transcription | journal = J. Biol. Chem. | volume = 284 | issue = 13 | pages = 8567–81 | date = March 2009 | pmid = 19176525 | pmc = 2659215 | doi = 10.1074/jbc.M808719200 }}
6. ^{{cite journal | vauthors = Leslie MC, Bar-Eli M | title = Regulation of gene expression in melanoma: new approaches for treatment | journal = J. Cell. Biochem. | volume = 94 | issue = 1 | pages = 25–38 | year = 2005 | pmid = 15523674 | doi = 10.1002/jcb.20296 }}
7. ^{{cite journal | vauthors = Papassava P, Gorgoulis VG, Papaevangeliou D, Vlahopoulos S, van Dam H, Zoumpourlis V | title = Overexpression of activating transcription factor-2 is required for tumor growth and progression in mouse skin tumors | journal = Cancer Res. | volume = 64 | issue = 23 | pages = 8573–84 | year = 2004 | pmid = 15574764 | doi = 10.1158/0008-5472.CAN-03-0955 }}
8. ^{{cite journal | vauthors = Vlahopoulos SA, Logotheti S, Mikas D, Giarika A, Gorgoulis V, Zoumpourlis V | title = The role of ATF-2 in oncogenesis | journal = BioEssays | volume = 30 | issue = 4 | pages = 314–27 | date = 17 March 2008 | pmid = 18348191 | doi = 10.1002/bies.20734 }}
9. ^{{cite journal | vauthors = Bhoumik A, Takahashi S, Breitweiser W, Shiloh Y, Jones N, Ronai Z | title = ATM-dependent phosphorylation of ATF2 is required for the DNA damage response | journal = Mol. Cell | volume = 18 | issue = 5 | pages = 577–87 | date = May 2005 | pmid = 15916964 | pmc = 2954254 | doi = 10.1016/j.molcel.2005.04.015 }}
10. ^{{cite journal | vauthors = Newell CL, Deisseroth AB, Lopez-Berestein G | title = Interaction of nuclear proteins with an AP-1/CRE-like promoter sequence in the human TNF-alpha gene | journal = J. Leukoc. Biol. | volume = 56 | issue = 1 | pages = 27–35 | date = July 1994 | pmid = 8027667 | doi = }}
11. ^{{cite journal | vauthors = Kara CJ, Liou HC, Ivashkiv LB, Glimcher LH | title = A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain | journal = Mol. Cell. Biol. | volume = 10 | issue = 4 | pages = 1347–57 | date = April 1990 | pmid = 2320002 | pmc = 362236 | doi = }}
12. ^{{cite journal | vauthors = Hai T, Curran T | title = Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 9 | pages = 3720–4 | date = May 1991 | pmid = 1827203 | pmc = 51524 | doi = 10.1073/pnas.88.9.3720 }}
13. ^{{cite journal | vauthors = Sano Y, Tokitou F, Dai P, Maekawa T, Yamamoto T, Ishii S | title = CBP alleviates the intramolecular inhibition of ATF-2 function | journal = J. Biol. Chem. | volume = 273 | issue = 44 | pages = 29098–105 | date = October 1998 | pmid = 9786917 | doi = 10.1074/jbc.273.44.29098 }}
14. ^1 {{cite journal | vauthors = Yamaguchi Y, Wada T, Suzuki F, Takagi T, Hasegawa J, Handa H | title = Casein kinase II interacts with the bZIP domains of several transcription factors | journal = Nucleic Acids Res. | volume = 26 | issue = 16 | pages = 3854–61 | date = August 1998 | pmid = 9685505 | pmc = 147779 | doi = 10.1093/nar/26.16.3854 }}
15. ^{{cite journal | vauthors = Murata T, Shinozuka Y, Obata Y, Yokoyama KK | title = Phosphorylation of two eukaryotic transcription factors, Jun dimerization protein 2 and activation transcription factor 2, in Escherichia coli by Jun N-terminal kinase 1 | journal = Anal. Biochem. | volume = 376 | issue = 1 | pages = 115–21 | date = May 2008 | pmid = 18307971 | doi = 10.1016/j.ab.2008.01.038 }}
16. ^1 {{cite journal | vauthors = Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ | title = Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine | journal = J. Biol. Chem. | volume = 270 | issue = 13 | pages = 7420–6 | date = March 1995 | pmid = 7535770 | doi = 10.1074/jbc.270.13.7420 }}
17. ^1 {{cite journal | vauthors = Chen Z, Cobb MH | title = Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2 | journal = J. Biol. Chem. | volume = 276 | issue = 19 | pages = 16070–5 | date = May 2001 | pmid = 11279118 | doi = 10.1074/jbc.M100681200 }}
18. ^1 {{cite journal | vauthors = Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ | title = Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 14 | pages = 7337–42 | date = July 1997 | pmid = 9207092 | pmc = 23822 | doi = 10.1073/pnas.94.14.7337 }}
19. ^{{cite journal | vauthors = Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z | title = c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors | journal = J. Biol. Chem. | volume = 272 | issue = 51 | pages = 32163–8 | date = December 1997 | pmid = 9405416 | doi = 10.1074/jbc.272.51.32163 }}
20. ^{{cite journal | vauthors = Sano Y, Harada J, Tashiro S, Gotoh-Mandeville R, Maekawa T, Ishii S | title = ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-beta signaling | journal = J. Biol. Chem. | volume = 274 | issue = 13 | pages = 8949–57 | date = March 1999 | pmid = 10085140 | doi = 10.1074/jbc.274.13.8949 }}
21. ^{{cite journal | vauthors = Hong S, Choi HM, Park MJ, Kim YH, Choi YH, Kim HH, Choi YH, Cheong J | title = Activation and interaction of ATF2 with the coactivator ASC-2 are responsive for granulocytic differentiation by retinoic acid | journal = J. Biol. Chem. | volume = 279 | issue = 17 | pages = 16996–7003 | date = April 2004 | pmid = 14734562 | doi = 10.1074/jbc.M311752200 }}
22. ^{{cite journal | vauthors = Cho SG, Bhoumik A, Broday L, Ivanov V, Rosenstein B, Ronai Z | title = TIP49b, a regulator of activating transcription factor 2 response to stress and DNA damage | journal = Mol. Cell. Biol. | volume = 21 | issue = 24 | pages = 8398–413 | date = December 2001 | pmid = 11713276 | pmc = 100004 | doi = 10.1128/MCB.21.24.8398-8413.2001 }}
23. ^{{cite journal | vauthors = Firestein R, Feuerstein N | title = 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 | journal = J. Biol. Chem. | volume = 273 | issue = 10 | pages = 5892–902 | date = March 1998 | pmid = 9488727 | doi = 10.1074/jbc.273.10.5892 }}

External links

  • {{UCSC gene info|ATF2}}

Further reading

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