WWTR1

WW domain containing transcription regulator 1
Identifiers
Symbols	WWTR1 ; TAZ
External IDs	OMIM: 607392 MGI: 1917649 HomoloGene: 9159 GeneCards: WWTR1 Gene
Gene ontology Molecular function • transcription coactivator activity • transcription corepressor activity • protein binding • protein homodimerization activity Cellular component • nucleus • nucleoplasm • transcription factor complex • cytoplasm • cytosol Biological process • negative regulation of transcription from RNA polymerase II promoter • osteoblast differentiation • negative regulation of protein phosphorylation • transcription, DNA-templated • regulation of transcription, DNA-templated • transcription initiation from RNA polymerase II promoter • negative regulation of protein kinase activity • transforming growth factor beta receptor signaling pathway • positive regulation of cell proliferation • gene expression • positive regulation of epithelial to mesenchymal transition • protein ubiquitination • stem cell division • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process • glomerulus development • multicellular organism growth • hippo signaling • negative regulation of catenin import into nucleus • negative regulation of fat cell differentiation • positive regulation of transcription from RNA polymerase II promoter • mesenchymal cell differentiation • cilium morphogenesis • regulation of SMAD protein import into nucleus • kidney morphogenesis • regulation of metanephric nephron tubule epithelial cell differentiation • negative regulation of canonical Wnt signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	25937	97064
Ensembl	ENSG00000018408	ENSMUSG00000027803
UniProt	Q9GZV5	Q9EPK5
RefSeq (mRNA)	NM_001168278	NM_001168281
RefSeq (protein)	NP_001161750	NP_001161753
Location (UCSC)	Chr 3: 149.52 – 149.74 Mb	Chr 3: 57.46 – 57.58 Mb
PubMed search

WW domain-containing transcription regulator protein 1 is a protein that in humans is encoded by the WWTR1 gene.^[1][2][3]

Function

WWTR1 It is a transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/LATS2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation. Regulates the nuclear accumulation of SMADs and has a key role in coupling them to the transcriptional machinery such as the mediator complex.

Using the human SHSY5Y cell line as a model of neuronal differentiation, human FAT1 was shown to regulate the nucleocytoplasmic relocation of WWTR1/TAZ and enhanced transcription of the Hippo target gene CTGF. The same study also showed FAT1 was able to regulate TGF-beta signalling ^[4]

References

1. Kanai F, Marignani PA, Sarbassova D, Yagi R, Hall RA, Donowitz M, Hisaminato A, Fujiwara T, Ito Y, Cantley LC, Yaffe MB (Dec 2000). "TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins". The EMBO Journal 19 (24): 6778–91. doi:10.1093/emboj/19.24.6778. PMC 305881. PMID 11118213.
2. Howell M, Borchers C, Milgram SL (Jun 2004). "Heterogeneous nuclear ribonuclear protein U associates with YAP and regulates its co-activation of Bax transcription". The Journal of Biological Chemistry 279 (25): 26300–6. doi:10.1074/jbc.M401070200. PMID 15096513.
3. "Entrez Gene: WWTR1 WW domain containing transcription regulator 1".
4. Ahmed AF, de Bock CE, Lincz LF, Pundavela J, Zouikr I, Sontag E, Hondermarck H, Thorne RF (Jun 2015). "FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation". Cellular and Molecular Life Sciences 72: 4653–69. doi:10.1007/s00018-015-1955-6. PMID 26104008.

Further reading

• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
• Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB (Aug 2005). "TAZ, a transcriptional modulator of mesenchymal stem cell differentiation". Science 309 (5737): 1074–8. doi:10.1126/science.1110955. PMID 16099986.
• Park KS, Whitsett JA, Di Palma T, Hong JH, Yaffe MB, Zannini M (Apr 2004). "TAZ interacts with TTF-1 and regulates expression of surfactant protein-C". The Journal of Biological Chemistry 279 (17): 17384–90. doi:10.1074/jbc.M312569200. PMID 14970209.