Biology:TEAD2

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

TEAD2 (ETF, ETEF-1, TEF-4), together with TEAD1, defines 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 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.[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]

Notes

References

  1. ↑ "Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1". Cell 65 (4): 551–68. May 1991. doi:10.1016/0092-8674(91)90088-g. PMID 1851669. 
  2. ↑ "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. September 1988. doi:10.1073/pnas.85.17.6404. PMID 3413104. Bibcode: 1988PNAS...85.6404M. 
  3. ↑ "The TEA domain: a novel, highly conserved DNA-binding motif". Cell 66 (1): 11–2. July 1991. doi:10.1016/0092-8674(91)90132-I. PMID 2070413. 
  4. ↑ "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. August 1995. doi:10.1074/jbc.270.31.18649. PMID 7629195. 
  5. ↑ "Transcription factor mTEAD-2 is selectively expressed at the beginning of zygotic gene expression in the mouse". Development 124 (10): 1963–73. May 1997. doi:10.1242/dev.124.10.1963. PMID 9169843. 
  6. ↑ "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. July 1990. doi:10.1128/mcb.10.7.3541. PMID 2192259. 
  7. ↑ "Isolation and physical characterization of three essential conidiation genes from Aspergillus nidulans". Molecular and Cellular Biology 7 (9): 3113–8. September 1987. doi:10.1128/mcb.7.9.3113. PMID 2823119. 
  8. ↑ "SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila". Current Biology 18 (6): 435–41. March 2008. doi:10.1016/j.cub.2008.02.034. PMID 18313299. 
  9. ↑ "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. 2007. doi:10.1387/ijdb.072375fn. PMID 17939122. 
  10. ↑ "Transcription factor TEAD2 is involved in neural tube closure". Genesis 45 (9): 577–87. September 2007. doi:10.1002/dvg.20330. PMID 17868131. 
  11. ↑ "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. September 1996. doi:10.1074/jbc.271.36.21775. PMID 8702974. 
  12. ↑ "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. May 2008. doi:10.1128/MCB.01759-07. PMID 18332127. 
  13. ↑ "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. May 2008. doi:10.1128/MCB.01759-07. PMID 18332127. 
  14. ↑ "Palmitoylation of TEAD Transcription Factors Is Required for Their Stability and Function in Hippo Pathway Signaling". Structure 24 (1): 179–86. January 2016. doi:10.1016/j.str.2015.11.005. PMID 26724994. 
  15. ↑ "Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1". Cell 65 (4): 551–68. May 1991. doi:10.1016/0092-8674(91)90088-g. PMID 1851669. 
  16. ↑ "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. October 2000. doi:10.1074/jbc.C000484200. PMID 10934189. 
  17. ↑ "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. June 1994. doi:10.1016/S0021-9258(19)89455-3. PMID 8206998. 
  18. ↑ "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. December 2002. doi:10.1074/jbc.M206858200. PMID 12376544. 
  19. ↑ "Structural basis of YAP recognition by TEAD4 in the hippo pathway". Genes & Development 24 (3): 290–300. February 2010. doi:10.1101/gad.1865310. PMID 20123908. 
  20. ↑ "Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD complexes". Structure 20 (7): 1135–40. July 2012. doi:10.1016/j.str.2012.04.004. PMID 22632831. 
  21. ↑ "The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members". The Biochemical Journal 388 (Pt 1): 217–25. May 2005. doi:10.1042/BJ20041434. PMID 15628970. 
  22. ↑ "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. May 2001. doi:10.1101/gad.888601. PMID 11358867. 
  23. ↑ "Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer". Cell 163 (4): 811–28. November 2015. doi:10.1016/j.cell.2015.10.044. PMID 26544935. 
  24. ↑ "The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version". Genes & Development 24 (9): 862–74. May 2010. doi:10.1101/gad.1909210. PMID 20439427. 
  25. ↑ "Transcription factor TEAD2 is involved in neural tube closure". Genesis 45 (9): 577–87. September 2007. doi:10.1002/dvg.20330. PMID 17868131. 

Further reading

External links



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