Insights into transcription enhancer factor 1 (TEF-1) activity from the solution structure of the TEA domain

Anbanandam, Asokan; Albarado, Diana C.; Nguyen, Cathy; Halder, Georg; Gao, Xiaolian; Veeraraghavan, Sudha

doi:10.1073/pnas.0607171103

Cited by 117 publications

(141 citation statements)

References 66 publications

(59 reference statements)

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“…The structure of the TEA DNA-binding domain of TEAD proteins has been determined previously (28). The structure of the YBD of TEAD is unknown, however.…”

Section: Resultsmentioning

confidence: 99%

Structural and functional analysis of the YAP-binding domain of human TEAD2

Tian¹,

Tomchick

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

150

178

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The Hippo pathway controls organ size and suppresses tumorigenesis in metazoans by blocking cell proliferation and promoting apoptosis. The TEAD1-4 proteins (which contain a DNA-binding domain but lack an activation domain) interact with YAP (which lacks a DNA-binding domain but contains an activation domain) to form functional heterodimeric transcription factors that activate proliferative and prosurvival gene expression programs. The Hippo pathway inhibits the YAP-TEAD hybrid transcription factors by phosphorylating and promoting cytoplasmic retention of YAP. Here we report the crystal structure of the YAP-binding domain (YBD) of human TEAD2. TEAD2 YBD adopts an immunoglobulin-like β-sandwich fold with two extra helix-turn-helix inserts. NMR studies reveal that the TEAD-binding domain of YAP is natively unfolded and that TEAD binding causes localized conformational changes in YAP. In vitro binding and in vivo functional assays define an extensive conserved surface of TEAD2 YBD as the YAP-binding site. Therefore, our studies suggest that a short segment of YAP adopts an extended conformation and forms extensive contacts with a rigid surface of TEAD. Targeting a surface-exposed pocket of TEAD might be an effective strategy to disrupt the YAP-TEAD interaction and to reduce the oncogenic potential of YAP.Hippo pathway | oncogene | crystallography

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“…The structure of the TEA DNA-binding domain of TEAD proteins has been determined previously (28). The structure of the YBD of TEAD is unknown, however.…”

Section: Resultsmentioning

confidence: 99%

Structural and functional analysis of the YAP-binding domain of human TEAD2

Tian¹,

Tomchick

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

150

178

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“…These findings provide several novel insights into the mechanisms that enable integration of TOR and MAPK kinase signaling in eukaryotic cells and ensure coordination of cell division and development. Importantly, our study pinpoints the connection between these two pathways to a transcriptional regulator of the TEA domain family, whose members are known to control development in many eukaryotes (Andrianopoulos and Timberlake 1991; Anbanandam et al 2006). Previous studies have described other connections between TOR and MAPK pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Our finding that repression of CLN1 gene expression by rapamycin involves Tec1 prompted us to test whether (Köhler et al 2002;Chou et al 2004;Anbanandam et al 2006;Chou et al 2006;Heise et al 2010). The location of the conserved PxY motifs for Rsp5 interaction is indicated, and the three motifs are shown in boldface type in the protein sequence below.…”

Section: Tec1 Is a Regulator Of Torc1 Controlled Chronological Lifespanmentioning

confidence: 99%

“…The shared components include the two MAPKs Fus3 and Kss1, the MAPK kinase Ste7, and the transcription factor Ste12, which positively control expression of both mating and vegetative adhesin genes (Roberts and Fink 1994). The program-specific components include the transcription factor Tec1, which belongs to the TEA domain (TEAD) family of transcriptional regulators, which control cellular development in many eukaryotes (Andrianopoulos and Timberlake 1991;Anbanandam et al 2006). In S. cerevisiae, Tec1 is required for adhesion and the expression of the vegetative adhesin gene FLO11 (Gavrias et al 1996;Mösch and Fink 1997;Lo and Dranginis 1998;Rupp et al 1999).…”

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confidence: 99%

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The TEA Transcription Factor Tec1 Links TOR and MAPK Pathways to Coordinate Yeast Development

et al. 2011

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In Saccharomyces cerevisiae, the TEA transcription factor Tec1 controls several developmental programs in response to nutrients and pheromones. Tec1 is targeted by the pheromone-responsive Fus3/Kss1 mitogen-activated protein kinase (MAPK) cascade, which destabilizes the transcription factor to ensure efficient mating of sexual partner cells. The regulation of Tec1 by signaling pathways that control cell division and development in response to nutrients, however, is not known. Here, we show that Tec1 protein stability is under control of the nutrient-sensitive target of rapamycin complex 1 (TORC1) signaling pathway via the Tip41-Tap42-Sit4 branch. We further show that degradation of Tec1 upon inhibition of TORC1 by rapamycin does not involve polyubiquitylation and appears to be proteasome independent. However, rapamycin-induced Tec1 degradation depends on the HECT ubiquitin ligase Rsp5, which physically interacts with Tec1 via conserved PxY motives. We further demonstrate that rapamycin and mating pheromone control Tec1 protein stability through distinct mechanisms by targeting different domains of the transcription factor. Finally, we show that Tec1 is a positive regulator of yeast chronological lifespan (CLS), a known TORC1-regulated process. Our findings indicate that in yeast, Tec1 links TORC1 and MAPK signaling pathways to coordinate control of cellular development in response to different stimuli.

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“…3,4 The TEA domain comprises a three-helix bundle with a homeodomain fold and binds a consensus MCAT (5 0 -CATTCCA/ T-3 0 ) element originally defined as the GT-II motif of the simian virus 40 (SV40) enhancer. 5 Mammalian TEADs are widely expressed with prominent expression in the nervous system and muscle. In-vitro, cell-based, knockout and transgenic studies have addressed the role of TEAD factors in regulation of muscle-expressed genes.…”

mentioning

confidence: 99%

Transcription factor TEAD4 regulates expression of Myogenin and the unfolded protein response genes during C2C12 cell differentiation

Benhaddou

Keime

et al. 2011

Cell Death Differ

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The TEAD (1-4) transcription factors comprise the conserved TEA/ATTS DNA-binding domain recognising the MCAT element in the promoters of muscle-specific genes. Despite extensive genetic analysis, the function of TEAD factors in muscle differentiation has proved elusive due to redundancy among the family members. Expression of the TEA/ATTS DNA-binding domain that acts as a dominant negative repressor of TEAD factors in C2C12 myoblasts inhibits their differentiation, whereas selective shRNA knockdown of TEAD4 results in abnormal differentiation characterised by the formation of shortened myotubes. Chromatin immunoprecipitation coupled to array hybridisation shows that TEAD4 occupies 867 promoters including those of myogenic miRNAs. We show that TEAD factors directly induce Myogenin, CDKN1A and Caveolin 3 expression to promote myoblast differentiation. RNA-seq identifies a set of genes whose expression is strongly reduced upon TEAD4 knockdown among which are structural and regulatory proteins and those required for the unfolded protein response. In contrast, TEAD4 represses expression of the growth factor CTGF (connective tissue growth factor) to promote differentiation. Together these results show that TEAD factor activity is essential for normal C2C12 cell differentiation and suggest a role for TEAD4 in regulating expression of the unfolded protein response genes. The TEAD transcription factors make a highly conserved family of 4 DNA-binding proteins 1,2 containing the TEA (Yeast (TEC-1), Aspergillus nidulans (AbaA) and Drosophilla (scalloped))/ATTS (Aspergillus nidulans (AbaA), Yeast (TEC-1), human TEF1, and Drosophilla (scalloped)) DNA-binding domain (DBD). 3,4 The TEA domain comprises a three-helix bundle with a homeodomain fold and binds a consensus MCAT (5 0 -CATTCCA/ T-3 0 ) element originally defined as the GT-II motif of the simian virus 40 (SV40) enhancer. 5 Mammalian TEADs are widely expressed with prominent expression in the nervous system and muscle. In-vitro, cell-based, knockout and transgenic studies have addressed the role of TEAD factors in regulation of muscle-expressed genes. 6-8 Cardiac troponin T, myosin, heavy polypeptide 7, cardiac muscle, beta (b-MHC) and Myocardin, have functional MCAT motifs in their regulatory regions. 2 Stimulation of a1-adrenergic signalling has been shown to induce cardiac hypertrophy and activate transcription of the b-MHC and skeletal a-actin genes in an MCAT-and TEAD-dependent manner in cultured neonatal rat cardiomyocytes. 9 Cardiac muscle-specific overexpression of TEAD4 in transgenic mice has been shown to induce arhythmias in vivo. 8 TEAD4 is specifically expressed in developing skeletal muscle in mouse embryos. 1 Chromatin immunoprecipitation-array hybridization (ChIP-chip) showed that TEAD4 is a direct target of the MYOD1 and MYOG transcription factors in C2C12 cells. 10 Although TEAD4 upregulation by MYOD1 and MYOG during differentiation is thought to activate transcription of muscle structural genes, mouse knockouts do not show any evident role for TEAD4 i...

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Insights into transcription enhancer factor 1 (TEF-1) activity from the solution structure of the TEA domain

Cited by 117 publications

References 66 publications

Structural and functional analysis of the YAP-binding domain of human TEAD2

Structural and functional analysis of the YAP-binding domain of human TEAD2

The TEA Transcription Factor Tec1 Links TOR and MAPK Pathways to Coordinate Yeast Development

Transcription factor TEAD4 regulates expression of Myogenin and the unfolded protein response genes during C2C12 cell differentiation

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