WWP1 explained
NEDD4-like E3 ubiquitin-protein ligase WWP1 is an enzyme that in humans is encoded by the WWP1 gene.[1] [2] [3]
Function
WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 4 tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. The encoded protein belongs to a family of NEDD4-like proteins, which are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Alternative splicing of this gene generates at least 6 transcript variants; however, the full length nature of these transcripts has not been defined. In neurons, murine ortholog Wwp1 and its homolog Wwp2 control polarity acquisition, formation, and branching of axons, as well as migration of newly born nerve cells into the cortical plate.[4]
Interactions
WWP1 has been shown to interact with:
Further reading
- Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery. . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
- Mosser EA, Kasanov JD, Forsberg EC, Kay BK, Ney PA, Bresnick EH . Physical and functional interactions between the transactivation domain of the hematopoietic transcription factor NF-E2 and WW domains. . Biochemistry . 37 . 39 . 13686–95 . 1998 . 9753456 . 10.1021/bi981310l .
- Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
- Conkright MD, Wani MA, Lingrel JB . Lung Krüppel-like factor contains an autoinhibitory domain that regulates its transcriptional activation by binding WWP1, an E3 ubiquitin ligase. . J. Biol. Chem. . 276 . 31 . 29299–306 . 2001 . 11375995 . 10.1074/jbc.M103670200 . free .
- Flasza M, Gorman P, Roylance R, Canfield AE, Baron M . Alternative splicing determines the domain structure of WWP1, a Nedd4 family protein. . Biochem. Biophys. Res. Commun. . 290 . 1 . 431–7 . 2002 . 11779188 . 10.1006/bbrc.2001.6206 .
- Galinier R, Gout E, Lortat-Jacob H, Wood J, Chroboczek J . Adenovirus protein involved in virus internalization recruits ubiquitin-protein ligases. . Biochemistry . 41 . 48 . 14299–305 . 2003 . 12450395 . 10.1021/bi020125b .
- Verdecia MA, Joazeiro CA, Wells NJ, Ferrer JL, Bowman ME, Hunter T, Noel JP . Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase. . Mol. Cell . 11 . 1 . 249–59 . 2003 . 12535537 . 10.1016/S1097-2765(02)00774-8 . free .
- Komuro A, Imamura T, Saitoh M, Yoshida Y, Yamori T, Miyazono K, Miyazawa K . Negative regulation of transforming growth factor-beta (TGF-beta) signaling by WW domain-containing protein 1 (WWP1). . Oncogene . 23 . 41 . 6914–23 . 2004 . 15221015 . 10.1038/sj.onc.1207885 . 7742985 . free .
- Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional proteomics mapping of a human signaling pathway. . Genome Res. . 14 . 7 . 1324–32 . 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
- Seo SR, Lallemand F, Ferrand N, Pessah M, L'Hoste S, Camonis J, Atfi A . The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2 for degradation. . EMBO J. . 23 . 19 . 3780–92 . 2005 . 15359284 . 522797 . 10.1038/sj.emboj.7600398 .
- 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 . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
- Chen C, Sun X, Guo P, Dong XY, Sethi P, Cheng X, Zhou J, Ling J, Simons JW, Lingrel JB, Dong JT . Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells. . J. Biol. Chem. . 280 . 50 . 41553–61 . 2006 . 16223724 . 10.1074/jbc.M506183200 . free .
- Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. . Cell . 125 . 4 . 801–14 . 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
- Flasza M, Nguyen Huu NS, Mazaleyrat S, Clémence S, Villemant C, Clarke R, Baron M . Regulation of the nuclear localization of the human Nedd4-related WWP1 protein by Notch. . Mol. Membr. Biol. . 23 . 3 . 269–76 . 2006 . 16785210 . 10.1080/09687860600665010 . 913524 .
- Laine A, Ronai Z . Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1. . Oncogene . 26 . 10 . 1477–83 . 2007 . 16924229 . 2997392 . 10.1038/sj.onc.1209924 .
- Chen C, Sun X, Guo P, Dong XY, Sethi P, Zhou W, Zhou Z, Petros J, Frierson HF, Vessella RL, Atfi A, Dong JT . Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer. . Oncogene . 26 . 16 . 2386–94 . 2007 . 17016436 . 10.1038/sj.onc.1210021 . 24487179 . free .
Notes and References
- Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM . Identification of novel human WW domain-containing proteins by cloning of ligand targets . J Biol Chem . 272 . 23 . 14611–6 . June 1997 . 9169421 . 10.1074/jbc.272.23.14611 . free .
- Wood JD, Yuan J, Margolis RL, Colomer V, Duan K, Kushi J, Kaminsky Z, Kleiderlein JJ, Sharp AH, Ross CA . Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins . Mol Cell Neurosci . 11 . 3 . 149–60 . July 1998 . 9647693 . 10.1006/mcne.1998.0677 . 20003277 . free .
- Web site: Entrez Gene: WWP1 WW domain containing E3 ubiquitin protein ligase 1.
- Ambrozkiewicz MC, Schwark M, Kishimoto-Suga M, Borisova E, Hori K, Salazar-Lázaro A, Rusanova A, Altas B, Piepkorn L, Bessa P, Schaub T, Zhang X, Rabe T, Ripamonti S, Rosário M, Akiyama H, Jahn O, Kobayashi T, Hoshino M, Tarabykin V, Kawabe H . Polarity Acquisition in Cortical Neurons Is Driven by Synergistic Action of Sox9-Regulated Wwp1 and Wwp2 E3 Ubiquitin Ligases and Intronic miR-140 . Neuron . 100 . 5 . 1097–1115.e15 . December 2018 . 30392800 . 10.1016/j.neuron.2018.10.008 . free.
- 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. Huda Zoghbi . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
- Conkright MD, Wani MA, Lingrel JB . Lung Krüppel-like factor contains an autoinhibitory domain that regulates its transcriptional activation by binding WWP1, an E3 ubiquitin ligase . J. Biol. Chem. . 276 . 31 . 29299–306 . August 2001 . 11375995 . 10.1074/jbc.M103670200 . free .
- Qin H, Pu HX, Li M, Ahmed S, Song J . Identification and structural mechanism for a novel interaction between a ubiquitin ligase WWP1 and Nogo-A, a key inhibitor for central nervous system regeneration . Biochemistry . 47 . 51 . 13647–58 . Dec 2008 . 19035836 . 10.1021/bi8017976 .