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E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Ubiquitinates ERBB4 isoforms JM-A CYT-1 and JM-B CYT-1, KLF2, KLF5 and TP63 and promotes their proteasomal degradation. Ubiquitinates RNF11 without targeting it for degradation. Ubiquitinates and promotes degradation of TGFBR1; the ubiquitination is enhanced by SMAD7. Ubiquitinates SMAD6 and SMAD7. Ubiquitinates and promotes degradation of SMAD2 in response to TGF-beta signaling, which requires interaction with TGIF.
Gene References into Functions
Study identified beta-dystroglycan as a substrate of WWP1 and found that the muscular dystrophy-causing mutation of WWP1 renders the enzyme hyperactive by relieving autoinhibition. PMID: 29635000
Results show that WWP1 is frequently upregulated in gastric cancer (GC) tissues and cells, and that its 3'-UTR is a putative target of miR-584 which suppresses its protein expression by mRNA degradation. PMID: 28431583
study describes a physical and functional interaction between Ebola virus VP40 (eVP40) and WWP1, a host E3 ubiquitin ligase that ubiquitinates VP40 and regulates virus-like particles egress. PMID: 28768865
Knock-down of WWP1 abrogates DNA damage-induced down-regulation of DeltaNp63alphaand partially rescues cell apoptosis PMID: 28426804
Describe an autoinhibitory mechanism for WWP1 ubiquitin ligase involving a linker-HECT domain interaction. This intramolecular interaction traps the HECT enzyme in its inactive state and can be relieved by linker phosphorylation. PMID: 28475870
results demonstrate that WWP1 catalyzes the formation of Ub chains through a sequential addition mechanism, in which Ub monomers are transferred in a successive fashion to the substrate, and that ubiquitination by WWP1 requires the presence of a low-affinity, noncovalent Ub-binding site within the HECT domain. PMID: 28461335
Study shows that WWP1 was upregulated in prostate cancer (PCa) clinical specimens and contributed to cancer cell invasion, indicating that this target of Mir-452 functioned as an oncogene. PMID: 27070713
Overexpression of WWP1 promotes tumorigenesis in patients with hepatocellular carcinoma. PMID: 26506518
PTPN14, a Pez mammalian homolog, is degraded by overexpressed Su(dx) or Su(dx) homologue WWP1 in mammalian cells. PMID: 25814387
miR-21 overexpression or WWP1 knockdown in endothelial progenitor cells significantly activates the TGFbeta signaling pathway and inhibits cell proliferation. PMID: 25755729
The cancer-driven alteration of WWP1 culminates in excessive TbetaRI degradation and attenuated TGFbeta1 cytostatic signaling, a consequence that could conceivably confer tumorigenic properties to WWP1. PMID: 26152726
Results suggest that elevated transcription and expression levels of ubiquitin ligase E3s WWP1, Smurf1 and Smurf2 genes may be the mechanisms of occurrence, development and metastasis of prostate cancer. PMID: 25051198
Most notably, WWP1 downregulation both inactivated PTEN-Akt signaling pathway in MKN-45 and AGS cells. our findings suggest that WWP1 acts as an oncogenic factor and should be considered as a novel interfering molecular target for gastric carcinoma PMID: 25293520
Data show that WWP1, which specifically ubiquitinates and degrades DeltaNp73 heterodimerizes with another E3 ligase, WWP2. PMID: 25071155
Knocking down WWP1 promoted cleaved caspase3 protein and p53 expression in hepatocellular carcinoma cells, and caspase3 inhibition could prevent cell apoptosis induced by the knockdown of WWP1. PMID: 24792179
results reveal that WWP1 might play an oncogenic role in oral cancer cells. PMID: 23849376
LATS1 is critical in mediating WWP1-induced increased cell proliferation in breast cancer cells. PMID: 23573293
WWP1 down-regulates AMPKalpha2 under high glucose culture conditions via the ubiquitin-proteasome pathway PMID: 23293026
WWP1 negatively regulates cell migration to CXCL12 by limiting CXCR4 degradation to promote breast cancer metastasis to bone. PMID: 22266093
WWP1 may function as the E3 ligase for several PY motif-containing proteins, such as Smad2, KLF5, p63, ErbB4/HER4, RUNX2, JunB, RNF11, SPG20, and Gag, as well as several non-PY motif containing proteins, such as TbetaR1, Smad4, KLF2, and EPS15. Review. PMID: 22051607
WWP1 depletion-induced apoptosis was rescued by the overexpression of the wild-type WWP1 but not the E3 ligase inactive WWP1-C890A mutant in MCF7 cells. PMID: 21480222
TAZ promotes breast cell growth partially through protecting KLF5 from WWP1-mediated degradation and enhancing KLF5's activities. PMID: 22045023
WWP1 mutations are not a common cause of human dystroglycanopathy. PMID: 21996799
WWP1 markedly inhibited the replicative senescence induced by p27(Kip1) by promoting p27(Kip1) degradation. PMID: 21795702
The authors show that WWP1 changes the ubiquitination status of ARRDC1, suggesting that the arrestins may provide a platform for ubiquitination in PPXY-dependent budding. PMID: 21191027
WWP1 regulates DeltaNp63 transcriptional activity, acting thus as a potential regulator of the proliferation and survival of epithelial-derived cells. PMID: 20951678
First demonstration of ubiquitin-protein ligase WWP1 from human lung cDNA library recruited by penton base proteins of human adenovirus serotypes Ad2 and Ad3 in vitro and in vivo. PMID: 12450395
Data show that the crystal structure of the HECT domain of the human ubiquitin ligase WWP1/AIP5 maintains a two-lobed structure like the HECT domain of the human ubiquitin ligase E6AP. PMID: 12535537
WWP1 negatively regulates TGF-beta signaling in cooperation with Smad7. PMID: 15221015
KLF5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells PMID: 16223724
Full-length expressed WWP1 could interact in vitro with the cytoplasmic domain of human Notch1, which also regulate the nuclear localization of WWP1. PMID: 16785210
these findings identify the first instance of a ubiquitin ligase that causes stabilization of p53 while inactivating its transcriptional activities. PMID: 16924229
WWP1 overexpression is a common mechanism involved in the inactivation of TGFbeta function in human cancer. PMID: 17016436
genomic aberrations of WWP1 may contribute to the pathogenesis of breast cancer PMID: 17330240
the interaction between Gag and WWP1 is required for functions other than Gag ubiquitination PMID: 17609263
WWP1 may promote cell proliferation and survival partially through suppressing RNF11-mediated ErbB2 and EGFR downregulation in human cancer cells. PMID: 18724389
WWP1 may have a context-dependent role in regulating cell survival through targeting different p63 proteins for degradation. PMID: 18806757
analysis of the interaction between ubiquitin ligase WWP1 and Nogo-A PMID: 19035836
WWP1 ubiquitinated and caused the degradation of HER4 but not of EGFR, HER2, or HER3. PMID: 19047365
Overexpression of WWP1 is associated with the estrogen receptor and insulin-like growth factor receptor 1 in breast carcinoma PMID: 19267401
Experiments suggest functions for WWP1 and SPG20 in the regulation of lipid droplet turnover and potential pathological mechanisms in Troyer syndrome. PMID: 19307600
WWP1 and its family members suppress the ErbB4 expression and function in breast cancer PMID: 19561640
Detected in heart, placenta, pancreas, kidney, liver, skeletal muscle, bone marrow, fetal brain, and at much lower levels in adult brain and lung. Isoform 1 and isoform 5 predominate in all tissues tested, except in testis and bone marrow, where isoform 5