TEAD2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTEAD2, ETF, TEAD-2, TEF-4, TEF4, TEA domain transcription factor 2
External IDsOMIM: 601729 MGI: 104904 HomoloGene: 19662 GeneCards: TEAD2
Orthologs
SpeciesHumanMouse
Entrez

8463

21677

Ensembl

ENSG00000074219

ENSMUSG00000030796

UniProt

Q15562

P48301

RefSeq (mRNA)

NM_001285498
NM_001285500
NM_011565
NM_001379272
NM_001379273

RefSeq (protein)

NP_001272427
NP_001272429
NP_035695
NP_001366201
NP_001366202

Location (UCSC)Chr 19: 49.34 – 49.36 MbChr 7: 44.87 – 44.88 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

TEAD2 (ETF, ETEF-1, TEF-4), together with TEAD1, defines a novel family of transcription factors, the TEAD family, highly conserved through evolution.[5][6] 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.[7] 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.[8] TEAD2 has also been shown to be expressed very early during development, i.e. from the 2-cell stage.[9]

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).[10] In Aspergillus nidulans, the TEA domain protein ABAA regulates the differentiation of conidiophores.[11] In drosophila the transcription factor Scalloped is involved in the development of the wing disc, survival and cell growth.[12] Finally in Xenopus, it has been demonstrated that the homolog of TEAD regulates muscle differentiation.[13]

Function

  • Regulation of mouse neural development[14]
  • Neuron proliferation[15]
  • Regulation of proliferation[16]
  • Regulation of apoptosis[17]

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.[18] 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.[19] Concerning TEAD2 very few studies have shown specific cofactors. But due to 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.[20]
  • 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.[21]
  • 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.[22]
  • The four Vestigial-like (VGLL) proteins are able to interact with all TEADs.[23] 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.[24]
  • 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.[25][26] 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.[27][28]

Clinical significance

Recent animal models indicating a possible association of TEAD2 with anencephaly.[29]

Notes

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000074219 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030796 - 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. ↑ Xiao JH, Davidson I, Matthes H, Garnier JM, Chambon P (May 1991). "Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1". Cell. 65 (4): 551–68. doi:10.1016/0092-8674(91)90088-g. PMID 1851669. S2CID 34258565.
  6. ↑ Mar JH, Ordahl CP (September 1988). "A conserved CATTCCT motif is required for skeletal muscle-specific activity of the cardiac troponin T gene promoter". Proceedings of the National Academy of Sciences of the United States of America. 85 (17): 6404–8. Bibcode:1988PNAS...85.6404M. doi:10.1073/pnas.85.17.6404. PMC 281980. PMID 3413104.
  7. ↑ Bürglin TR (July 1991). "The TEA domain: a novel, highly conserved DNA-binding motif". Cell. 66 (1): 11–2. doi:10.1016/0092-8674(91)90132-I. PMID 2070413. S2CID 2819591.
  8. ↑ Yasunami M, Suzuki K, Houtani T, Sugimoto T, Ohkubo H (August 1995). "Molecular characterization of cDNA encoding a novel protein related to transcriptional enhancer factor-1 from neural precursor cells". The Journal of Biological Chemistry. 270 (31): 18649–54. doi:10.1074/jbc.270.31.18649. PMID 7629195.
  9. ↑ Kaneko KJ, Cullinan EB, Latham KE, DePamphilis ML (May 1997). "Transcription factor mTEAD-2 is selectively expressed at the beginning of zygotic gene expression in the mouse". Development. 124 (10): 1963–73. doi:10.1242/dev.124.10.1963. PMID 9169843.
  10. ↑ Laloux I, Dubois E, Dewerchin M, Jacobs E (July 1990). "TEC1, a gene involved in the activation of Ty1 and Ty1-mediated gene expression in Saccharomyces cerevisiae: cloning and molecular analysis". Molecular and Cellular Biology. 10 (7): 3541–50. doi:10.1128/mcb.10.7.3541. PMC 360789. PMID 2192259.
  11. ↑ Boylan MT, Mirabito PM, Willett CE, Zimmerman CR, Timberlake WE (September 1987). "Isolation and physical characterization of three essential conidiation genes from Aspergillus nidulans". Molecular and Cellular Biology. 7 (9): 3113–8. doi:10.1128/mcb.7.9.3113. PMC 367944. PMID 2823119.
  12. ↑ Goulev Y, Fauny JD, Gonzalez-Marti B, Flagiello D, Silber J, Zider A (March 2008). "SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila". Current Biology. 18 (6): 435–41. doi:10.1016/j.cub.2008.02.034. PMID 18313299. S2CID 16369642.
  13. ↑ Naye F, Tréguer K, Soulet F, Faucheux C, Fédou S, Thézé N, Thiébaud P (2007). "Differential expression of two TEF-1 (TEAD) genes during Xenopus laevis development and in response to inducing factors". The International Journal of Developmental Biology. 51 (8): 745–52. doi:10.1387/ijdb.072375fn. PMID 17939122.
  14. ↑ Kaneko KJ, Kohn MJ, Liu C, DePamphilis ML (September 2007). "Transcription factor TEAD2 is involved in neural tube closure". Genesis. 45 (9): 577–87. doi:10.1002/dvg.20330. PMC 2765819. PMID 17868131.
  15. ↑ Jacquemin P, Hwang JJ, Martial JA, Dollé P, Davidson I (September 1996). "A novel family of developmentally regulated mammalian transcription factors containing the TEA/ATTS DNA binding domain". The Journal of Biological Chemistry. 271 (36): 21775–85. doi:10.1074/jbc.271.36.21775. PMID 8702974.
  16. ↑ Sawada A, Kiyonari H, Ukita K, Nishioka N, Imuta Y, Sasaki H (May 2008). "Redundant roles of Tead1 and Tead2 in notochord development and the regulation of cell proliferation and survival". Molecular and Cellular Biology. 28 (10): 3177–89. doi:10.1128/MCB.01759-07. PMC 2423158. PMID 18332127.
  17. ↑ Sawada A, Kiyonari H, Ukita K, Nishioka N, Imuta Y, Sasaki H (May 2008). "Redundant roles of Tead1 and Tead2 in notochord development and the regulation of cell proliferation and survival". Molecular and Cellular Biology. 28 (10): 3177–89. doi:10.1128/MCB.01759-07. PMC 2423158. PMID 18332127.
  18. ↑ Noland CL, Gierke S, Schnier PD, Murray J, Sandoval WN, Sagolla M, Dey A, Hannoush RN, Fairbrother WJ, Cunningham CN (January 2016). "Palmitoylation of TEAD Transcription Factors Is Required for Their Stability and Function in Hippo Pathway Signaling". Structure. 24 (1): 179–86. doi:10.1016/j.str.2015.11.005. PMID 26724994.
  19. ↑ Xiao JH, Davidson I, Matthes H, Garnier JM, Chambon P (May 1991). "Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1". Cell. 65 (4): 551–68. doi:10.1016/0092-8674(91)90088-g. PMID 1851669. S2CID 34258565.
  20. ↑ Belandia B, Parker MG (October 2000). "Functional interaction between the p160 coactivator proteins and the transcriptional enhancer factor family of transcription factors". The Journal of Biological Chemistry. 275 (40): 30801–5. doi:10.1074/jbc.C000484200. PMID 10934189.
  21. ↑ MacLellan WR, Lee TC, Schwartz RJ, Schneider MD (June 1994). "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". The Journal of Biological Chemistry. 269 (24): 16754–60. doi:10.1016/S0021-9258(19)89455-3. PMID 8206998.
  22. ↑ Maeda T, Chapman DL, Stewart AF (December 2002). "Mammalian vestigial-like 2, a cofactor of TEF-1 and MEF2 transcription factors that promotes skeletal muscle differentiation". The Journal of Biological Chemistry. 277 (50): 48889–98. doi:10.1074/jbc.M206858200. PMID 12376544.
  23. ↑ Chen L, Chan SW, Zhang X, Walsh M, Lim CJ, Hong W, Song H (February 2010). "Structural basis of YAP recognition by TEAD4 in the hippo pathway". Genes & Development. 24 (3): 290–300. doi:10.1101/gad.1865310. PMC 2811830. PMID 20123908.
  24. ↑ Pobbati AV, Chan SW, Lee I, Song H, Hong W (July 2012). "Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD complexes". Structure. 20 (7): 1135–40. doi:10.1016/j.str.2012.04.004. PMID 22632831.
  25. ↑ Mahoney WM, Hong JH, Yaffe MB, Farrance IK (May 2005). "The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members". The Biochemical Journal. 388 (Pt 1): 217–25. doi:10.1042/BJ20041434. PMC 1186710. PMID 15628970.
  26. ↑ Vassilev A, Kaneko KJ, Shu H, Zhao Y, DePamphilis ML (May 2001). "TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm". Genes & Development. 15 (10): 1229–41. doi:10.1101/gad.888601. PMC 313800. PMID 11358867.
  27. ↑ Yu FX, Zhao B, Guan KL (November 2015). "Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer". Cell. 163 (4): 811–28. doi:10.1016/j.cell.2015.10.044. PMC 4638384. PMID 26544935.
  28. ↑ Zhao B, Li L, Lei Q, Guan KL (May 2010). "The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version". Genes & Development. 24 (9): 862–74. doi:10.1101/gad.1909210. PMC 2861185. PMID 20439427.
  29. ↑ Kaneko KJ, Kohn MJ, Liu C, DePamphilis ML (September 2007). "Transcription factor TEAD2 is involved in neural tube closure". Genesis. 45 (9): 577–87. doi:10.1002/dvg.20330. PMC 2765819. PMID 17868131.

Further reading

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