WWTR1
WWTR1 (WW domain-containing transcription regulator protein 1) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Ovarian cancer, Breast cancer and Skin cancer.
Overview
Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signalling pathway that plays a pivotal role in organ size control and tumour 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.
Open Targets scores its association with cancer at 0.65 (direct and indirect evidence; datatypes affected pathway 0.25, literature 0.99, genetic association 0.00, somatic mutation 0.98, animal model 0.53). IntOGen calls it a driver in 1 cohort (1 activating, 0 loss-of-function), covering Ovarian Epithelial Tumour.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · WWTR1 (WW domain-containing transcription regulator protein 1) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Ovarian cancer, Breast cancer and Skin cancer.
- 1 · What it is
WWTR1 (WW domain-containing transcription regulator protein 1) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Ovarian cancer, Breast cancer and Skin cancer.
- 2 · What goes wrong in cancer
Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signalling pathway that plays a pivotal role in organ size control and tumour suppression by restricting proliferation and promoting apoptosis.
- 3 · How drugs use it
No product in this corpus aims at WWTR1 yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
External identifiers
Sources: HGNC HGNC:24042 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9GZV5 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000018408 (association with cancer (MONDO_0004992) 0.65; per-cancer scores at or above 0.5: skin cancer 0.52, breast cancer 0.55 (GraphQL API, CC0)); IntOGen WWTR1 (driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signalling pathway that plays a pivotal role in organ size control and tumour 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. In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation. Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex. Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition. Location: Nucleus; Cytoplasm; Cell membrane; Cell junction, tight junction (UniProt). Locus 3q25.1 (HGNC).
- Ovarian cancer: IntOGen driver in 1 cohort (OVT)
- Breast cancer: Open Targets association 0.55 with breast cancer (MONDO_0007254)
- Skin cancer: Open Targets association 0.52 with skin cancer (MONDO_0002898)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"WWTR1" OR ABSTRACT:"WWTR1" OR TITLE:"WW domain containing transcription regulator 1" OR ABSTRACT:"WW domain containing transcription regulator 1" OR TITLE:"WW domain-containing transcription regulator protein 1" OR ABSTRACT:"WW domain-containing transcription regulator protein 1" OR TITLE:"DKFZp586I1419" OR ABSTRACT:"DKFZp586I1419") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about WWTR1, not a curated reading list.