YAP1- and WWTR1 (TAZ)-stimulated gene expression (Homo sapiens)

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1, 25, 775, 7, 91, 3, 4, 8110cytosolnucleoplasmTBL1X YAP1TBX5 Peroxisome Proliferator Receptor Element (PPRE) CTGF geneHELZ2 AA HIPK2 EPA TEAD3 GATA4 KAT2B TBX5RXRA WWTR1 NCOA2 CHD9 TEAD1 TGS1 ALA RUNX2:WWTR1(TAZ)TEAD2 NPPA(1-153)TEAD1 TEAD3 WWTR1 Palm KAT2BTEADNKX2-5:GATA4:HIPK1,2RUNX2TBX5:WWTR1:PCAFPPARA NKX2-5 RUNX2 YAP1 TEAD1 CTGFTEAD3 NCOA1 CARM1 LINA MED1 TEAD4 TEAD2 TEAD:YAP1NPPA geneCREBBP TEAD4 PPARA:RXRACoactivator complexNCOA6 TEAD:WWTR1(TAZ)TEAD2 WWTR1TBL1XR1 HIPK1 TEAD4 WWTR1 SMARCD3 7165, 7


Description

YAP1 and WWTR1 (TAZ) are transcriptional co-activators, both homologues of the Drosophila Yorkie protein. They both interact with members of the TEAD family of transcription factors, and WWTR1 interacts as well with TBX5 and RUNX2, to promote gene expression. Their transcriptional targets include genes critical to regulation of cell proliferation and apoptosis. Their subcellular location is regulated by the Hippo signaling cascade: phosphorylation mediated by this cascade leads to the cytosolic sequestration of both proteins (Murakami et al. 2005; Oh and Irvine 2010). View original pathway at:Reactome.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114969view16:49, 25 January 2021ReactomeTeamReactome version 75
113413view11:48, 2 November 2020ReactomeTeamReactome version 74
112615view15:59, 9 October 2020ReactomeTeamReactome version 73
101531view11:40, 1 November 2018ReactomeTeamreactome version 66
101066view21:22, 31 October 2018ReactomeTeamreactome version 65
100596view19:56, 31 October 2018ReactomeTeamreactome version 64
100145view16:41, 31 October 2018ReactomeTeamreactome version 63
99695view15:10, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99283view12:46, 31 October 2018ReactomeTeamreactome version 62
93910view13:44, 16 August 2017ReactomeTeamreactome version 61
93486view11:24, 9 August 2017ReactomeTeamreactome version 61
87190view08:26, 19 July 2016EgonwOntology Term : 'regulatory pathway' added !
86582view09:21, 11 July 2016ReactomeTeamreactome version 56
83145view10:09, 18 November 2015ReactomeTeamVersion54
81495view13:02, 21 August 2015ReactomeTeamVersion53
76971view08:26, 17 July 2014ReactomeTeamFixed remaining interactions
76676view12:04, 16 July 2014ReactomeTeamFixed remaining interactions
76004view10:06, 11 June 2014ReactomeTeamRe-fixing comment source
75710view11:05, 10 June 2014ReactomeTeamReactome 48 Update
75064view13:57, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74708view08:47, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AA MetaboliteCHEBI:15843 (ChEBI)
ALA MetaboliteCHEBI:27432 (ChEBI)
CARM1 ProteinQ86X55 (Uniprot-TrEMBL)
CHD9 ProteinQ3L8U1 (Uniprot-TrEMBL)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CTGF geneGeneProductENSG00000118523 (Ensembl)
CTGFProteinP29279 (Uniprot-TrEMBL)
EPA MetaboliteCHEBI:28364 (ChEBI)
GATA4 ProteinP43694 (Uniprot-TrEMBL)
HELZ2 ProteinQ9BYK8 (Uniprot-TrEMBL)
HIPK1 ProteinQ86Z02 (Uniprot-TrEMBL)
HIPK2 ProteinQ9H2X6 (Uniprot-TrEMBL)
KAT2B ProteinQ92831 (Uniprot-TrEMBL)
KAT2BProteinQ92831 (Uniprot-TrEMBL)
LINA MetaboliteCHEBI:17351 (ChEBI)
MED1 ProteinQ15648 (Uniprot-TrEMBL) MED1 is a component of each of the various Mediator complexes, that function as transcription co-activators. The MED1-containing compolexes include the DRIP, ARC, TRIP and CRSP compllexes.
NCOA1 ProteinQ15788 (Uniprot-TrEMBL)
NCOA2 ProteinQ15596 (Uniprot-TrEMBL)
NCOA6 ProteinQ14686 (Uniprot-TrEMBL)
NKX2-5 ProteinP52952 (Uniprot-TrEMBL)
NKX2-5:GATA4:HIPK1,2ComplexR-HSA-5578875 (Reactome)
NPPA geneGeneProductENSG00000175206 (Ensembl)
NPPA(1-153)ProteinP01160 (Uniprot-TrEMBL)
PPARA ProteinQ07869 (Uniprot-TrEMBL)
PPARA:RXRA Coactivator complexComplexR-HSA-400154 (Reactome)
Palm MetaboliteCHEBI:15756 (ChEBI)
Peroxisome Proliferator Receptor Element (PPRE) R-NUL-422139 (Reactome) Peroxisome proliferator receptor elements bind heterodimers containing a peroxisome proliferator receptor and a retinoic acid receptor. The consensus sequence is TGAMCTTTGNCCTAGWTYYG.
RUNX2 ProteinQ13950 (Uniprot-TrEMBL)
RUNX2:WWTR1(TAZ)ComplexR-HSA-2064919 (Reactome)
RUNX2ProteinQ13950 (Uniprot-TrEMBL)
RXRA ProteinP19793 (Uniprot-TrEMBL)
SMARCD3 ProteinQ6STE5 (Uniprot-TrEMBL)
TBL1X ProteinO60907 (Uniprot-TrEMBL)
TBL1XR1 ProteinQ9BZK7 (Uniprot-TrEMBL)
TBX5 ProteinQ99593 (Uniprot-TrEMBL)
TBX5:WWTR1:PCAFComplexR-HSA-2032799 (Reactome)
TBX5ProteinQ99593 (Uniprot-TrEMBL)
TEAD1 ProteinP28347 (Uniprot-TrEMBL)
TEAD2 ProteinQ15562 (Uniprot-TrEMBL)
TEAD3 ProteinQ99594 (Uniprot-TrEMBL)
TEAD4 ProteinQ15561 (Uniprot-TrEMBL)
TEAD:WWTR1(TAZ)ComplexR-HSA-2032762 (Reactome)
TEAD:YAP1ComplexR-HSA-2032772 (Reactome)
TEADComplexR-HSA-2032773 (Reactome)
TGS1 ProteinQ96RS0 (Uniprot-TrEMBL)
WWTR1 ProteinQ9GZV5 (Uniprot-TrEMBL)
WWTR1ProteinQ9GZV5 (Uniprot-TrEMBL)
YAP1 ProteinP46937 (Uniprot-TrEMBL)
YAP1ProteinP46937 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
CTGF geneR-HSA-1989766 (Reactome)
CTGFArrowR-HSA-1989766 (Reactome)
KAT2BR-HSA-2032794 (Reactome)
NKX2-5:GATA4:HIPK1,2ArrowR-HSA-2032800 (Reactome)
NPPA geneR-HSA-2032800 (Reactome)
NPPA(1-153)ArrowR-HSA-2032800 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1989766 (Reactome)
R-HSA-1989766 (Reactome) The CTGF gene is transcribed to yield mRNA and the mRNA is translated to yield protein. Transcription of the CTGF gene is increased by both YAP1:TEAD and WWTR1(TAZ):TEAD transcriptional coactivator:transcription factor complexes, so that CTFG is one of the many genes whose expression is downregulated by the action of the hippo cascade (Zhang et al. 2009; Zhao et al. 2008).
R-HSA-2032775 (Reactome) In the nucleus the YAP1 transcriptional coactivator can bind any one of the four TEAD transcription factors to form a complex. The stoichiometry of this complex is unknown (Chan et al. 2009).
R-HSA-2032781 (Reactome) In the nucleus the WWTR1 (TAZ) transcriptional coactivator can bind any one of the four TEAD transcription factors to form a complex. The stoichiometry of this complex is unknown (Chan et al. 2009; Zhang et al. 2009).
R-HSA-2032794 (Reactome) In the nucleus the WWTR1 (TAZ) transcriptional coactivator can bind the TBX5 transcription factor and PCAF (KAT2B) histone acetyltransferase to form a complex. The stoichiometry of this complex is unknown (Murakami et al. 2005).
R-HSA-2032800 (Reactome) Transcription of the NPPA (ANF) gene is stimulated by the action of a transcription factor complex that includes WWTR1 (TAZ), TBX5, and the PCAF (KAT2B) histone acetyltransferase (Murakami et al. 2005). Homeobox protein NKX-2.5 (NKX2-5), in cooperation with transcription factor GATA-4 (GATA4) and interacting partners homeodomain-interacting protein kinase 1 and 2 (HIPK1 and 2), acts as a transcriptional activator factor of NPPA in mice (Lee et al. 1998). Defects in NKX2-5 can cause diverse cardiac developmental disorders (Schott et al. 1998, Benson et al. 1999).
R-HSA-2064932 (Reactome) In the nucleus the WWTR1 (TAZ) transcriptional coactivator can bind the RUNX2 transcription factor to form a complex. This interaction has not been experimentally characterized in human cells but is inferred from properties of the homologous mouse proteins. The stoichiometry of this complex is unknown (Cui et al. 2003).
RUNX2:WWTR1(TAZ)ArrowR-HSA-2064932 (Reactome)
RUNX2R-HSA-2064932 (Reactome)
TBX5:WWTR1:PCAFArrowR-HSA-2032794 (Reactome)
TBX5:WWTR1:PCAFArrowR-HSA-2032800 (Reactome)
TBX5R-HSA-2032794 (Reactome)
TEAD:WWTR1(TAZ)ArrowR-HSA-1989766 (Reactome)
TEAD:WWTR1(TAZ)ArrowR-HSA-2032781 (Reactome)
TEAD:YAP1ArrowR-HSA-1989766 (Reactome)
TEAD:YAP1ArrowR-HSA-2032775 (Reactome)
TEADR-HSA-2032775 (Reactome)
TEADR-HSA-2032781 (Reactome)
WWTR1R-HSA-2032781 (Reactome)
WWTR1R-HSA-2032794 (Reactome)
WWTR1R-HSA-2064932 (Reactome)
YAP1R-HSA-2032775 (Reactome)
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