Transcriptional enhancer factor TEF-1 also known as TEA domain family member 1 (TEAD1) and transcription factor 13 (TCF-13) is a protein that in humans is encoded by the TEAD1gene.[5][6][7][8] TEAD1 was the first member of the TEAD family of transcription factors to be identified.[5][9]
Structure
All members of the TEAD family share a highly conserved DNA binding domain called the TEA domain.[10] This DNA binding domain has a consensus DNA sequence 5’-CATTCCA/T-3’ that is called the MCAT element.[11] The three dimensional structure of the TEA domain has been identified.[9] Its conformation is close to that of the homeodomain and contains 3 α helixes (H1, H2 and H3). It is the H3 helix that enables TEAD proteins to bind DNA.[12]
Another conserved domain of TEAD1 is located at the C terminus of the protein. It allows the binding of cofactors and has been called the YAP1 binding domain, because it is its ability to bind this well-known TEAD proteins co-factor that led to its identification. Indeed, TEAD proteins cannot induce gene expression on their own. They have to associate with cofactors to be able to act[13]
Tissue distribution
TEAD1 is expressed in various tissues including skeletal muscle, pancreas, placenta, lung, and heart.[14][15][16][17][18][19][20]
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).[21] In Aspergillus nidulans, the TEA domain protein ABAA regulates the differentiation of conidiophores.[22] In drosophila the transcription factor Scalloped is involved in the development of the wing disc, survival and cell growth.[23] Finally in Xenopus it has been demonstrated that the ortholog of TEAD1 regulates muscle differentiation.[24]
Function
Heart development (myocardium differentiation,[25]
Skeletal muscle development (alpha-actin of skeletal muscles),[26][27][28])
Smooth muscle development (alpha-actin of smooth muscles),[26][29]
Regulation of myosin heavy chain genes,[30] cardiac muscular genes troponin T and I [9]
Protein Kinase A (pKA) can phosphorylate TEAD1 at serine 102, after the TEA domain. This phosphorylation is needed for the transcriptional activation of the α MyHC gene.[36] Protein Kinase C (pKC) phosphorylates TEAD1 on serine and threonine next to the last alpha loop in the TEA domain. This phosphorylation decreases TEAD1 binding to the GTIIC enhancer.[37]
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.[38]
Cofactors
TEAD proteins require cofactors to induce the transcription of target genes.[14] TEAD1 interacts with all members of the SRC family of steroid receptor coactivators. In HeLa cells TEAD1 and SRC induce gene expression,[39] TEAD1 interacts with PARP (poly (ADP-ribose) polymerase) to regulate smooth muscle α-actin expression. PARP can also ADP-ribosylate the TEAD proteins and make the chromatin context favorable to transcription through histone modification,[40] SRF (Serum response factor) and TEAD1 together regulate gene expression.[41]
TEAD proteins and MEF2 (myocyte enhancer factor 2) interact physically. The binding of MEF2 on DNA induces and potentiates TEAD1 recruitment at MCAT sequences that are adjacent to MEF2 binding sites. This recruitment leads to the repression of the MLC2v (Myosin Light Chain 2 v) and βMHC ( β-myosin heavy chain ) promoter.[42] TEAD1 and the phosphoprotein MAX interact in vivo and in vitro. Once this complex is formed, these two proteins can regulate the alpha-myosin heavy chain (α-MHC) gene expression.[43]
The four Vestigial-like (VGLL) proteins are able to interact with all TEADs.[44] 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 [45] Moreover, VGLL2 interaction with TEAD1 activates muscle promoter upon C2C12 differentiation and enhances MyoD-mediated myogenic in 10T1/2.[46] Finally the complex TEAD/VGLL4 acts as a default transcriptional repressor.[47]
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.[47][48] 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.[31][49]
Role in cancer
Analysis of cancer transcriptome databases (www.ebi.ac.uk/gxa) showed that TEAD1 is dysregulated in several types of cancers. First in Kaposi sarcoma there is a 300-fold increase in TEAD1 levels. Moreover, the increase of TEAD expression can be detected in basal-like breast cancers,[50][51] fallopian tube carcinoma,[52] and germ cell tumors.[53] Otherwise, in other types of cancer TEAD expression is decreased, for example in other breast cancer types and in renal or bladder cancers. This dual role can be explained by the different targets and the differential regulation of target genes by TEAD transcription factors.[35][54] Finally recent studies showed that TEAD1 and YAP in ovarian cancer can induces cell stemness and chemoresistance.[55] and that genetic variant of TEAD protein and YAP are enriched in some cancers.[56]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abXiao 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. PMID1851669. S2CID34258565.
^Jacquemin P, Depetris D, Mattei MG, Martial JA, Davidson I (Jan 1999). "Localization of human transcription factor TEF-4 and TEF-5 (TEAD2, TEAD3) genes to chromosomes 19q13.3 and 6p21.2 using fluorescence in situ hybridization and radiation hybrid analysis". Genomics. 55 (1): 127–9. doi:10.1006/geno.1998.5628. hdl:2268/13836. PMID9889009.
^Azakie A, Lamont L, Fineman JR, He Y (December 2005). "Divergent transcriptional enhancer factor-1 regulates the cardiac troponin T promoter". American Journal of Physiology. Cell Physiology. 289 (6): C1522–34. doi:10.1152/ajpcell.00126.2005. PMID16049055.
^ abXiao 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. PMID1851669. S2CID34258565.
^Stewart AF, Richard CW, Suzow J, Stephan D, Weremowicz S, Morton CC, Adra CN (October 1996). "Cloning of human RTEF-1, a transcriptional enhancer factor-1-related gene preferentially expressed in skeletal muscle: evidence for an ancient multigene family". Genomics. 37 (1): 68–76. doi:10.1006/geno.1996.0522. PMID8921372.
^Yasunami M, Suzuki K, Ohkubo H (November 1996). "A novel family of TEA domain-containing transcription factors with distinct spatiotemporal expression patterns". Biochemical and Biophysical Research Communications. 228 (2): 365–70. doi:10.1006/bbrc.1996.1667. PMID8920920.
^Azakie A, Lamont L, Fineman JR, He Y (December 2005). "Divergent transcriptional enhancer factor-1 regulates the cardiac troponin T promoter". American Journal of Physiology. Cell Physiology. 289 (6): C1522-34. doi:10.1152/ajpcell.00126.2005. PMID16049055.
^Swartz EA, Johnson AD, Owens GK (August 1998). "Two MCAT elements of the SM alpha-actin promoter function differentially in SM vs. non-SM cells". The American Journal of Physiology. 275 (2 Pt 1): C608-18. doi:10.1152/ajpcell.1998.275.2.C608. PMID9688616.
^Gupta MP, Gupta M, Dizon E, Zak R (1996). "Sympathetic control of cardiac myosin heavy chain gene expression". Molecular and Cellular Biochemistry. 157 (1–2): 117–24. doi:10.1007/bf00227889. PMID8739237. S2CID10103037.
^Han W, Jung EM, Cho J, Lee JW, Hwang KT, Yang SJ, Kang JJ, Bae JY, Jeon YK, Park IA, Nicolau M, Jeffrey SS, Noh DY (June 2008). "DNA copy number alterations and expression of relevant genes in triple-negative breast cancer". Genes, Chromosomes & Cancer. 47 (6): 490–9. doi:10.1002/gcc.20550. PMID18314908. S2CID24749682.
Fossdal R, Magnússon L, Weber JL, Jensson O (March 1995). "Mapping the locus of atrophia areata, a helicoid peripapillary chorioretinal degeneration with autosomal dominant inheritance, to chromosome 11p15". Human Molecular Genetics. 4 (3): 479–83. doi:10.1093/hmg/4.3.479. PMID7795606.
Stewart AF, Richard CW, Suzow J, Stephan D, Weremowicz S, Morton CC, Adra CN (October 1996). "Cloning of human RTEF-1, a transcriptional enhancer factor-1-related gene preferentially expressed in skeletal muscle: evidence for an ancient multigene family". Genomics. 37 (1): 68–76. doi:10.1006/geno.1996.0522. PMID8921372.
Vaudin P, Delanoue R, Davidson I, Silber J, Zider A (November 1999). "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". Development. 126 (21): 4807–16. doi:10.1242/dev.126.21.4807. PMID10518497.
Maeda T, Gupta MP, Stewart AF (June 2002). "TEF-1 and MEF2 transcription factors interact to regulate muscle-specific promoters". Biochemical and Biophysical Research Communications. 294 (4): 791–7. doi:10.1016/S0006-291X(02)00556-9. PMID12061776.
Thompson M, Andrade VA, Andrade SJ, Pusl T, Ortega JM, Goes AM, Leite MF (February 2003). "Inhibition of the TEF/TEAD transcription factor activity by nuclear calcium and distinct kinase pathways". Biochemical and Biophysical Research Communications. 301 (2): 267–74. doi:10.1016/S0006-291X(02)03024-3. PMID12565854.