Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling

Ota, Masahiro; Sasaki, Hiroshi

doi:10.1242/dev.027151

Cited by 348 publications

(373 citation statements)

References 62 publications

(76 reference statements)

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“…A homologue of Yap1, Taz, shares redundant functions such as controlling cell proliferation and sensing mechanical stress [14,15]. Furthermore, Tead proteins-important in TE differentiation during early embryogenesis, form a complex with Yap1 and are known to activate their downstream target genes [16,17].…”

Section: Introductionmentioning

confidence: 99%

Yap1 is dispensable for self‐renewal but required for proper differentiation of mouse embryonic stem ( ES ) cells

et al. 2016

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Yap1 is a transcriptional co-activator of the Hippo pathway. The importance of Yap1 in early cell fate decision during embryogenesis has been well established, though its role in embryonic stem (ES) cells remains elusive. Here, we report that Yap1 plays crucial roles in normal differentiation rather than self-renewal of ES cells. Yap1-depleted ES cells maintain undifferentiated state with a typical colony morphology as well as robust alkaline phosphatase activity. These cells also retain comparable levels of the core pluripotent factors, such as Pou5f1 and Sox2, to the levels in wild-type ES cells without significant alteration of lineage-specific marker genes. Conversely, overexpression of Yap1 in ES cells promotes nuclear translocation of Yap1, resulting in disruption of self-renewal and triggering differentiation by up-regulating lineage-specific genes. Moreover, Yap1-deficient ES cells show impaired induction of lineage markers during differentiation. Collectively, our data demonstrate that Yap1 is a required factor for proper differentiation of mouse ES cells, while remaining dispensable for self-renewal.

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Section: Introductionmentioning

confidence: 99%

Yap1 is dispensable for self‐renewal but required for proper differentiation of mouse embryonic stem ( ES ) cells

et al. 2016

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“…In mammals, the structure and function of TEAD-YAP were well characterized [26][27][28]. Recent studies revealed that mammalian TEAD proteins are involved in the regulation of cell proliferation by cooperating with YAP under the control of Hpo signaling [29][30][31][32]. Interestingly, both genetic studies in Drosophila and pharmacological studies in transgenic mice revealed that loss of sd or inhibition of TEAD has minimal impact on normal tissue homeostasis and physiology, suggesting that Sd/TEAD is required for Yki/YAP-mediated tissue overgrowth but is largely dispensable for normal tissue homeostasis [15,16,33].…”

Section: Introductionmentioning

confidence: 99%

A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity

Guo

et al. 2013

Cell Res

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The Hippo (Hpo) pathway controls tissue growth and organ size by regulating the activity of transcriptional co-activator Yorkie (Yki), which associates with transcription factor Scalloped (Sd) in the nucleus to promote downstream target gene expression. Here we identify a novel protein Sd-Binding-Protein (SdBP)/Tgi, which directly competes with Yki for binding to Sd through its TDU domains and inhibits the Sd-Yki transcriptional activity. We also find that SdBP retains Yki in the nucleus through the association with Yki WW domains via its PPXY motifs. Collectively, we identify SdBP as a novel component of the Hpo pathway, negatively regulating the transcriptional activity of SdYki to restrict tissue growth.

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“…Similar to the fly pathway, the effectors of the mammalian Hippo pathway are transcription factors, including YAP (Yes-associated protein), and TEAD, the mammalian homologs of Yki and Sd, respectively (16,18,22,23). There are four closely related human TEAD proteins, TEAD1-4.…”

mentioning

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.

146

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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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Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling

Cited by 348 publications

References 62 publications

Yap1 is dispensable for self‐renewal but required for proper differentiation of mouse embryonic stem ( ES ) cells

Yap1 is dispensable for self‐renewal but required for proper differentiation of mouse embryonic stem ( ES ) cells

A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity

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

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