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词条 TEAD2
释义

  1. Function

  2. Tissue distribution

  3. TEAD orthologs

  4. Function

  5. Post transcriptional modifications

  6. Cofactors

  7. Clinical significance

  8. References

  9. Further reading

  10. External links

{{Infobox_gene}}TEAD2 (ETF, ETEF-1, TEF-4), together with TEAD1, defined a novel family of transcription factors, the TEAD family, highly conserved through evolution.[1][2]

TEAD proteins were notably found in Drosophila (Scalloped), C. elegans (egl -44), S. cerevisiae and A. nidulans.

TEAD2 has been less studied than TEAD1 but a few studies revealed its role during development.

Function

TEAD2 is a member of the mammalian TEAD transcription factor family (initially named the transcriptional enhancer factor (TEF) family), which contain the TEA/ATTS DNA-binding domain.[3] Members of the family in mammals are TEAD1, TEAD2, TEAD3, TEAD4.

Tissue distribution

TEAD2 is selectively expressed in a subset of embryonic tissues including the cerebellum, testis, and distal portions of the forelimb and hindlimb buds, as well as the tail bud, but it is essentially absent from adult tissues.[4] TEAD2 has also been shown to be expressed very early during development, i.e. from the 2-cell stage.[5]

TEAD orthologs

TEAD proteins are found in many organisms under different names, assuming different functions.

For example, in Saccharomyces cerevisiae TEC-1 regulates the transposable element TY1 and is involved in pseudohyphale growth (the elongated shape that yeasts take when grown in nutrient-poor conditions).[6]

In Aspergillus nidulans, the TEA domain protein ABAA regulates the differentiation of conidiophores.[7]

In drosophila the transcription factor Scalloped is involved in the development of the wing disc, survival and cell growth.[8]

Finally in Xenopus, it has been demonstrated that the homolog of TEAD regulates muscle differentiation.[9]

Function

  • Regulation of mouse neural development[10]
  • Neuron proliferation[11]
  • Regulation of proliferation[12]
  • Regulation of apoptosis[13]

Post transcriptional modifications

TEAD1 can be palmitoylated on a conserved cysteine at the C-term of the protein. This post-translational modification is critical for proper folding of TEAD proteins and their stability.[14]

Based on bioinformatics evidence TEAD2 can be ubiquitinylated at Lys75 and several phosphorylation sites exist in the protein.

Cofactors

TEAD transcription factors have to associate with cofactors to be able to induce the transcription of target genes.[15] Concerning TEAD2 very few studies have shown specific cofactors. But due the high homology between the TEAD family members its believed that TEAD proteins may share cofactors. Here are presented the cofactor that interact with TEAD2.

  • TEAD2 interacts with all members of the SRC family of steroid receptor coactivators. It has been shown in HeLa cells that TEAD2 and SRC induce gene expression.[16]
  • SRF (Serum response factor) and TEAD2 interact through their DNA binding domain, respectively the MADS domain and the TEA domain. In vitro studies demonstrated that this interaction leads to the activation of the skeletal muscle α-actin promoter.[17]
  • TEAD proteins and MEF2 (myocyte enhancer factor 2) interact physically. The binding of MEF2 on the DNA induces and potentiates TEAD2 recruitment at MCAT sequences that are adjacent to MEF2 binding sites.[18]
  • The four Vestigial-like (VGLL) proteins are able to interact with all TEADs.[19] The precise function of TEAD and VGLL interaction is still poorly understood. It has been shown that TEAD/VGLL1 complexes promote anchorage-independent cell proliferation in prostate cancer cell lines suggesting a role in cancer progression.[20]
  • The interaction between YAP (Yes Associated Protein 65), TAZ, a transcriptional coactivator paralog to YAP, and all TEAD proteins was demonstrated both in vitro and in vivo. In both cases the interaction of the proteins leads to increased TEAD transcriptional activity.[21][22] YAP/TAZ are effectors of the Hippo tumor suppressor pathway that restricts organ growth by keeping in check cell proliferation and promoting apoptosis in mammals and also in Drosophila.[23][24]

Clinical significance

Recent animal models indicating a possible association of TEAD2 with anencephaly.[25]

References

1. ^{{cite journal | vauthors = Xiao JH, Davidson I, Matthes H, Garnier JM, Chambon P | title = Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1 | journal = Cell | volume = 65 | issue = 4 | pages = 551–68 | date = May 1991 | pmid = 1851669 | doi=10.1016/0092-8674(91)90088-g}}
2. ^{{cite journal | vauthors = Mar JH, Ordahl CP | title = A conserved CATTCCT motif is required for skeletal muscle-specific activity of the cardiac troponin T gene promoter | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 17 | pages = 6404–8 | date = September 1988 | pmid = 3413104 | doi=10.1073/pnas.85.17.6404 | pmc=281980}}
3. ^{{cite journal | vauthors = Bürglin TR | title = The TEA domain: a novel, highly conserved DNA-binding motif | journal = Cell | volume = 66 | issue = 1 | pages = 11–2 | date = July 1991 | pmid = 2070413 | pmc = | doi = 10.1016/0092-8674(91)90132-I }}
4. ^{{cite journal | vauthors = Yasunami M, Suzuki K, Houtani T, Sugimoto T, Ohkubo H | title = Molecular characterization of cDNA encoding a novel protein related to transcriptional enhancer factor-1 from neural precursor cells | journal = The Journal of Biological Chemistry | volume = 270 | issue = 31 | pages = 18649–54 | date = August 1995 | pmid = 7629195 | doi=10.1074/jbc.270.31.18649}}
5. ^{{cite journal | vauthors = Kaneko KJ, Cullinan EB, Latham KE, DePamphilis ML | title = Transcription factor mTEAD-2 is selectively expressed at the beginning of zygotic gene expression in the mouse | journal = Development | volume = 124 | issue = 10 | pages = 1963–73 | date = May 1997 | pmid = 9169843 }}
6. ^{{cite journal | vauthors = Laloux I, Dubois E, Dewerchin M, Jacobs E | title = TEC1, a gene involved in the activation of Ty1 and Ty1-mediated gene expression in Saccharomyces cerevisiae: cloning and molecular analysis | journal = Molecular and Cellular Biology | volume = 10 | issue = 7 | pages = 3541–50 | date = July 1990 | pmid = 2192259 | doi=10.1128/mcb.10.7.3541 | pmc=360789}}
7. ^{{cite journal | vauthors = Boylan MT, Mirabito PM, Willett CE, Zimmerman CR, Timberlake WE | title = Isolation and physical characterization of three essential conidiation genes from Aspergillus nidulans | journal = Molecular and Cellular Biology | volume = 7 | issue = 9 | pages = 3113–8 | date = September 1987 | pmid = 2823119 | doi=10.1128/mcb.7.9.3113 | pmc=367944}}
8. ^{{cite journal | vauthors = Goulev Y, Fauny JD, Gonzalez-Marti B, Flagiello D, Silber J, Zider A | title = SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila | journal = Current Biology | volume = 18 | issue = 6 | pages = 435–41 | date = March 2008 | pmid = 18313299 | doi = 10.1016/j.cub.2008.02.034 }}
9. ^{{cite journal | vauthors = Naye F, Tréguer K, Soulet F, Faucheux C, Fédou S, Thézé N, Thiébaud P | title = Differential expression of two TEF-1 (TEAD) genes during Xenopus laevis development and in response to inducing factors | journal = The International Journal of Developmental Biology | volume = 51 | issue = 8 | pages = 745–52 | date = 2007 | pmid = 17939122 | doi = 10.1387/ijdb.072375fn }}
10. ^{{cite journal | vauthors = Kaneko KJ, Kohn MJ, Liu C, DePamphilis ML | title = Transcription factor TEAD2 is involved in neural tube closure | journal = Genesis | volume = 45 | issue = 9 | pages = 577–87 | date = September 2007 | pmid = 17868131 | doi = 10.1002/dvg.20330 | pmc=2765819}}
11. ^{{cite journal | vauthors = Jacquemin P, Hwang JJ, Martial JA, Dollé P, Davidson I | title = A novel family of developmentally regulated mammalian transcription factors containing the TEA/ATTS DNA binding domain | journal = The Journal of Biological Chemistry | volume = 271 | issue = 36 | pages = 21775–85 | date = September 1996 | pmid = 8702974 | doi=10.1074/jbc.271.36.21775}}
12. ^{{cite journal | vauthors = Sawada A, Kiyonari H, Ukita K, Nishioka N, Imuta Y, Sasaki H | title = Redundant roles of Tead1 and Tead2 in notochord development and the regulation of cell proliferation and survival | journal = Molecular and Cellular Biology | volume = 28 | issue = 10 | pages = 3177–89 | date = May 2008 | pmid = 18332127 | doi = 10.1128/MCB.01759-07 | pmc=2423158}}
13. ^{{cite journal | vauthors = Sawada A, Kiyonari H, Ukita K, Nishioka N, Imuta Y, Sasaki H | title = Redundant roles of Tead1 and Tead2 in notochord development and the regulation of cell proliferation and survival | journal = Molecular and Cellular Biology | volume = 28 | issue = 10 | pages = 3177–89 | date = May 2008 | pmid = 18332127 | doi = 10.1128/MCB.01759-07 | pmc=2423158}}
14. ^{{cite journal | vauthors = Noland CL, Gierke S, Schnier PD, Murray J, Sandoval WN, Sagolla M, Dey A, Hannoush RN, Fairbrother WJ, Cunningham CN | title = Palmitoylation of TEAD Transcription Factors Is Required for Their Stability and Function in Hippo Pathway Signaling | journal = Structure | volume = 24 | issue = 1 | pages = 179–86 | date = January 2016 | pmid = 26724994 | doi = 10.1016/j.str.2015.11.005 }}
15. ^{{cite journal | vauthors = Xiao JH, Davidson I, Matthes H, Garnier JM, Chambon P | title = Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1 | journal = Cell | volume = 65 | issue = 4 | pages = 551–68 | date = May 1991 | pmid = 1851669 | doi=10.1016/0092-8674(91)90088-g}}
16. ^{{cite journal | vauthors = Belandia B, Parker MG | title = Functional interaction between the p160 coactivator proteins and the transcriptional enhancer factor family of transcription factors | journal = The Journal of Biological Chemistry | volume = 275 | issue = 40 | pages = 30801–5 | date = October 2000 | pmid = 10934189 | doi = 10.1074/jbc.C000484200 }}
17. ^{{cite journal | vauthors = MacLellan WR, Lee TC, Schwartz RJ, Schneider MD | title = Transforming growth factor-beta response elements of the skeletal alpha-actin gene. Combinatorial action of serum response factor, YY1, and the SV40 enhancer-binding protein, TEF-1 | journal = The Journal of Biological Chemistry | volume = 269 | issue = 24 | pages = 16754–60 | date = June 1994 | pmid = 8206998 }}
18. ^{{cite journal | vauthors = Maeda T, Chapman DL, Stewart AF | title = Mammalian vestigial-like 2, a cofactor of TEF-1 and MEF2 transcription factors that promotes skeletal muscle differentiation | journal = The Journal of Biological Chemistry | volume = 277 | issue = 50 | pages = 48889–98 | date = December 2002 | pmid = 12376544 | doi = 10.1074/jbc.M206858200 }}
19. ^{{cite journal | vauthors = Chen L, Chan SW, Zhang X, Walsh M, Lim CJ, Hong W, Song H | title = Structural basis of YAP recognition by TEAD4 in the hippo pathway | journal = Genes & Development | volume = 24 | issue = 3 | pages = 290–300 | date = February 2010 | pmid = 20123908 | doi = 10.1101/gad.1865310 | pmc=2811830}}
20. ^{{cite journal | vauthors = Pobbati AV, Chan SW, Lee I, Song H, Hong W | title = Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD complexes | journal = Structure | volume = 20 | issue = 7 | pages = 1135–40 | date = July 2012 | pmid = 22632831 | doi = 10.1016/j.str.2012.04.004 }}
21. ^{{cite journal | vauthors = Mahoney WM, Hong JH, Yaffe MB, Farrance IK | title = The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members | journal = The Biochemical Journal | volume = 388 | issue = Pt 1 | pages = 217–25 | date = May 2005 | pmid = 15628970 | doi = 10.1042/BJ20041434 | pmc=1186710}}
22. ^{{cite journal | vauthors = Vassilev A, Kaneko KJ, Shu H, Zhao Y, DePamphilis ML | title = TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm | journal = Genes & Development | volume = 15 | issue = 10 | pages = 1229–41 | date = May 2001 | pmid = 11358867 | doi = 10.1101/gad.888601 | pmc=313800}}
23. ^{{cite journal | vauthors = Yu FX, Zhao B, Guan KL | title = Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer | journal = Cell | volume = 163 | issue = 4 | pages = 811–28 | date = November 2015 | pmid = 26544935 | doi = 10.1016/j.cell.2015.10.044 }}
24. ^{{cite journal | vauthors = Zhao B, Li L, Lei Q, Guan KL | title = The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version | journal = Genes & Development | volume = 24 | issue = 9 | pages = 862–74 | date = May 2010 | pmid = 20439427 | doi = 10.1101/gad.1909210 | pmc=2861185}}
25. ^{{cite journal | vauthors = Kaneko KJ, Kohn MJ, Liu C, DePamphilis ML | title = Transcription factor TEAD2 is involved in neural tube closure | journal = Genesis | volume = 45 | issue = 9 | pages = 577–87 | date = September 2007 | pmid = 17868131 | pmc = 2765819 | doi = 10.1002/dvg.20330 }}

Further reading

{{refbegin|33em}}
  • {{cite journal | vauthors = Vaudin P, Delanoue R, Davidson I, Silber J, Zider A | title = TONDU (TDU), a novel human protein related to the product of vestigial (vg) gene of Drosophila melanogaster interacts with vertebrate TEF factors and substitutes for Vg function in wing formation | journal = Development | volume = 126 | issue = 21 | pages = 4807–16 | date = November 1999 | pmid = 10518497 | doi = }}
  • {{cite journal | vauthors = Zhao B, Ye X, Yu J, Li L, Li W, Li S, Yu J, Lin JD, Wang CY, Chinnaiyan AM, Lai ZC, Guan KL | title = TEAD mediates YAP-dependent gene induction and growth control | journal = Genes & Development | volume = 22 | issue = 14 | pages = 1962–71 | date = July 2008 | pmid = 18579750 | pmc = 2492741 | doi = 10.1101/gad.1664408 }}
  • {{cite journal | vauthors = Belandia B, Parker MG | title = Functional interaction between the p160 coactivator proteins and the transcriptional enhancer factor family of transcription factors | journal = The Journal of Biological Chemistry | volume = 275 | issue = 40 | pages = 30801–5 | date = October 2000 | pmid = 10934189 | doi = 10.1074/jbc.C000484200 }}
  • {{cite journal | vauthors = Tian W, Yu J, Tomchick DR, Pan D, Luo X | title = Structural and functional analysis of the YAP-binding domain of human TEAD2 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 16 | pages = 7293–8 | date = April 2010 | pmid = 20368466 | pmc = 2867681 | doi = 10.1073/pnas.1000293107 }}
  • {{cite journal | vauthors = Zhang H, Liu CY, Zha ZY, Zhao B, Yao J, Zhao S, Xiong Y, Lei QY, Guan KL | title = TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition | journal = The Journal of Biological Chemistry | volume = 284 | issue = 20 | pages = 13355–62 | date = May 2009 | pmid = 19324877 | pmc = 2679435 | doi = 10.1074/jbc.M900843200 }}
  • {{cite journal | vauthors = Vassilev A, Kaneko KJ, Shu H, Zhao Y, DePamphilis ML | title = TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm | journal = Genes & Development | volume = 15 | issue = 10 | pages = 1229–41 | date = May 2001 | pmid = 11358867 | pmc = 313800 | doi = 10.1101/gad.888601 }}
{{refend}}

External links

  • {{MeshName|TEAD2+protein,+human}}
{{Transcription factors|g3}}

1 : Transcription factors
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