WWTR1

WWTR1 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 STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 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. It regulates the nuclear accumulation of SMADS and has a key role in coupling them to the transcriptional machinery such as the mediator complex. It regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition.

Full Name

WW domain containing transcription regulator 1

Function

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 (PubMed:11118213, PubMed:18227151).
The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18227151).
WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation (PubMed:19010321).
In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:18568018).
Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex (PubMed:18568018).
Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition (PubMed:18227151, PubMed:18568018).

Biological Process

Biological Process cilium assembly Source:Ensembl
Biological Process glomerulus development Source:Ensembl
Biological Process heart process Source:Ensembl
Biological Process hippo signaling Source:UniProtKB1 Publication
Biological Process kidney morphogenesis Source:Ensembl
Biological Process mesenchymal cell differentiation Source:Ensembl
Biological Process multicellular organism growth Source:Ensembl
Biological Process negative regulation of canonical Wnt signaling pathway Source:BHF-UCL1 Publication
Biological Process negative regulation of fat cell differentiation Source:ARUK-UCL1 Publication
Biological Process negative regulation of protein kinase activity Source:BHF-UCL1 Publication
Biological Process negative regulation of protein phosphorylation Source:BHF-UCL1 Publication
Biological Process negative regulation of transcription by RNA polymerase II Source:Ensembl
Biological Process osteoblast differentiation Source:Ensembl
Biological Process positive regulation of cell population proliferation Source:UniProtKB1 Publication
Biological Process positive regulation of epithelial to mesenchymal transition Source:UniProtKB1 Publication
Biological Process positive regulation of osteoblast differentiation Source:ARUK-UCL1 Publication
Biological Process positive regulation of protein localization to nucleus Source:UniProtKB
Biological Process positive regulation of transcription by RNA polymerase II Source:GO_Central1 Publication
Biological Process protein ubiquitination Source:Ensembl
Biological Process regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process regulation of metanephric nephron tubule epithelial cell differentiation Source:Ensembl
Biological Process regulation of SMAD protein signal transduction Source:UniProtKB1 Publication
Biological Process SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source:Ensembl
Biological Process stem cell division Source:UniProtKB1 Publication
Biological Process tissue homeostasis Source:Ensembl

Cellular Location

Nucleus
Cytoplasm
Cell membrane
Concentrates along specific portions of the plasma membrane, and accumulates in punctate nuclear bodies (By similarity).
When phosphorylated, is retained in the cytoplasm by YWHAZ (By similarity).
Can be retained in the nucleus by MED15 (PubMed:18568018).
Localized in the cytoplasm in areas of epithelial cell high density (PubMed:21145499).
At blastocyst stage expressed in the nucleus in trophectodermal cells, however expressed in the cytoplasm in the inner cell mass (By similarity).

PTM

Phosphorylated by LATS2 and STK3/MST2. Phosphorylation by LATS2 results in creation of 14-3-3 binding sites, retention in the cytoplasm, and functional inactivation. Phosphorylation results in the inhibition of transcriptional coactivation through YWHAZ-mediated nuclear export.