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 2 WW domains and a short-chain dehydrogenase/reductase domain (SRD). The highest normal expression of this gene is detected in hormonally regulated tissues such as testis, ovary, and prostate. This expression pattern and the presence of an SRD domain suggest a role for this gene in steroid metabolism. The encoded protein is more than 90% identical to the mouse protein, which is an essential mediator of tumor necrosis factor-alpha-induced apoptosis, suggesting a similar, important role in apoptosis for the human protein. In addition, there is evidence that this gene behaves as a suppressor of tumor growth. Alternative splicing of this gene generates transcript variants that encode different isoforms.[8]
WWOX is also known as human accelerated region 6. It may, therefore, have played a key role in differentiating humans from apes.[9]
^ abcGRCh38: Ensembl release 89: ENSG00000186153 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000004637 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Bednarek AK, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM (May 2000). "WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer". Cancer Res. 60 (8): 2140–5. PMID 10786676.
^Ried K, Finnis M, Hobson L, Mangelsdorf M, Dayan S, Nancarrow JK, Woollatt E, Kremmidiotis G, Gardner A, Venter D, Baker E, Richards RI (Sep 2000). "Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells". Hum Mol Genet. 9 (11): 1651–63. doi:10.1093/hmg/9.11.1651. PMID 10861292.
^Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Feb 2009). "The SDR (Short-Chain Dehydrogenase/Reductase and Related Enzymes) Nomenclature Initiative". Chem Biol Interact. 178 (1–3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC2896744. PMID 19027726.
^Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, Haussler D (2006-08-16). "An RNA gene expressed during cortical development evolved rapidly in humans" (PDF). Nature. 443 (7108): 167–72. Bibcode:2006Natur.443..167P. doi:10.1038/nature05113. PMID 16915236. S2CID 18107797. supplement
^Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N (February 2001). "Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity". J. Biol. Chem. 276 (5): 3361–70. doi:10.1074/jbc.M007140200. PMID 11058590.
^Mahajan NP, Whang YE, Mohler JL, Earp HS (November 2005). "Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox". Cancer Res. 65 (22): 10514–23. CiteSeerX10.1.1.322.9333. doi:10.1158/0008-5472.can-05-1127. PMID 16288044.
Further readingEdit
Ramos D, Aldaz CM (2006). "WWOX, a Chromosomal Fragile Site Gene and its Role in Cancer". New trends in cancer for the 21st century. Advances in Experimental Medicine and Biology. Vol. 587. pp. 149–59. doi:10.1007/978-1-4020-5133-3_14. ISBN978-1-4020-4966-8. PMID 17163164.
Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N (2001). "Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity". J. Biol. Chem. 276 (5): 3361–70. doi:10.1074/jbc.M007140200. PMID 11058590.
Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, Scott D, Porteous DJ, Smyth JF, Gabra H, Watson JE (2001). "WWOX: A candidate tumor suppressor gene involved in multiple tumor types". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11417–22. Bibcode:2001PNAS...9811417P. doi:10.1073/pnas.191175898. PMC58744. PMID 11572989.
Bednarek AK, Keck-Waggoner CL, Daniel RL, Laflin KJ, Bergsagel PL, Kiguchi K, Brenner AJ, Aldaz CM (2001). "WWOX, the FRA16D gene, behaves as a suppressor of tumor growth". Cancer Res. 61 (22): 8068–73. PMID 11719429.
Kuroki T, Trapasso F, Shiraishi T, Alder H, Mimori K, Mori M, Croce CM (2002). "Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma". Cancer Res. 62 (8): 2258–60. PMID 11956080.
Chang NS, Doherty J, Ensign A (2003). "JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis". J. Biol. Chem. 278 (11): 9195–202. doi:10.1074/jbc.M208373200. PMID 12514174.
Ludes-Meyers JH, Bednarek AK, Popescu NC, Bedford M, Aldaz CM (2004). "WWOX, the common chromosomal fragile site, FRA16D, cancer gene". Cytogenet. Genome Res. 100 (1–4): 101–10. doi:10.1159/000072844. PMC4150470. PMID 14526170.
Watanabe A, Hippo Y, Taniguchi H, Iwanari H, Yashiro M, Hirakawa K, Kodama T, Aburatani H (2004). "An opposing view on WWOX protein function as a tumor suppressor". Cancer Res. 63 (24): 8629–33. PMID 14695174.
Chen ST, Chuang JI, Wang JP, Tsai MS, Li H, Chang NS (2004). "Expression of WW domain-containing oxidoreductase WOX1 in the developing murine nervous system". Neuroscience. 124 (4): 831–9. doi:10.1016/j.neuroscience.2003.12.036. PMID 15026124. S2CID 14784743.
Ishii H, Mimori K, Vecchione A, Sutheesophon K, Fujiwara T, Mori M, Furukawa Y (2004). "Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX". Biochem. Biophys. Res. Commun. 316 (4): 1088–93. doi:10.1016/j.bbrc.2004.02.159. PMID 15044096.
Ludes-Meyers JH, Kil H, Bednarek AK, Drake J, Bedford MT, Aldaz CM (2004). "WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins". Oncogene. 23 (29): 5049–55. doi:10.1038/sj.onc.1207680. PMC4143251. PMID 15064722.
Aqeilan RI, Pekarsky Y, Herrero JJ, Palamarchuk A, Letofsky J, Druck T, Trapasso F, Han SY, Melino G, Huebner K, Croce CM (2004). "Functional association between Wwox tumor suppressor protein and p73, a p53 homolog". Proc. Natl. Acad. Sci. U.S.A. 101 (13): 4401–6. Bibcode:2004PNAS..101.4401A. doi:10.1073/pnas.0400805101. PMC384759. PMID 15070730.
Kuroki T, Yendamuri S, Trapasso F, Matsuyama A, Aqeilan RI, Alder H, Rattan S, Cesari R, Nolli ML, Williams NN, Mori M, Kanematsu T, Croce CM (2004). "The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis". Clin. Cancer Res. 10 (7): 2459–65. doi:10.1158/1078-0432.CCR-03-0096. PMID 15073125.
Guler G, Uner A, Guler N, Han SY, Iliopoulos D, Hauck WW, McCue P, Huebner K (2004). "The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma". Cancer. 100 (8): 1605–14. doi:10.1002/cncr.20137. PMID 15073846. S2CID 23157412.
Sze CI, Su M, Pugazhenthi S, Jambal P, Hsu LJ, Heath J, Schultz L, Chang NS (2004). "Down-regulation of WW domain-containing oxidoreductase induces Tau phosphorylation in vitro. A potential role in Alzheimer's disease". J. Biol. Chem. 279 (29): 30498–506. doi:10.1074/jbc.M401399200. PMID 15126504.
Aqeilan RI, Kuroki T, Pekarsky Y, Albagha O, Trapasso F, Baffa R, Huebner K, Edmonds P, Croce CM (2004). "Loss of WWOX expression in gastric carcinoma". Clin. Cancer Res. 10 (9): 3053–8. doi:10.1158/1078-0432.CCR-03-0594. PMID 15131042.
Park SW, Ludes-Meyers J, Zimonjic DB, Durkin ME, Popescu NC, Aldaz CM (2004). "Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma". Br. J. Cancer. 91 (4): 753–9. doi:10.1038/sj.bjc.6602023. PMC2364795. PMID 15266310.
This article on a gene on human chromosome 16 is a stub. You can help Wikipedia by expanding it.
wwox, domain, containing, oxidoreductase, enzyme, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes1wmvidentifiersaliases, d16s432e, fra16d, hhcma56, pro0128, scar12, sdr41c1, wox1, eiee28, domain, containing, oxidore. WW domain containing oxidoreductase is an enzyme that in humans is encoded by the WWOX gene 5 6 7 8 WWOXAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes1WMVIdentifiersAliasesWWOX D16S432E FOR FRA16D HHCMA56 PRO0128 SCAR12 SDR41C1 WOX1 EIEE28 WW domain containing oxidoreductase DEE28External IDsOMIM 605131 MGI 1931237 HomoloGene 56334 GeneCards WWOXGene location Human Chr Chromosome 16 human 1 Band16q23 1 q23 2Start78 099 400 bp 1 End79 212 667 bp 1 Gene location Mouse Chr Chromosome 8 mouse 2 Band8 8 E1Start115 166 395 bp 2 End116 079 447 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inparotid glandoptic nerveglomerulussural nervemetanephric glomerulusendothelial cellkidney tubuleexternal globus pallidusinferior olivary nucleusventral tegmental areaTop expressed ininterventricular septumamygdalavisual cortexcerebellar cortexsecondary oocytespermatocytemirroradrenal glandsuperior frontal gyrusproximal tubuleMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functiontranscription coactivator activity protein dimerization activity protein binding enzyme binding oxidoreductase activityCellular componentcytoplasm cytosol Golgi apparatus plasma membrane microvillus RNA polymerase II transcription regulator complex mitochondrion nucleusBiological processcellular response to transforming growth factor beta stimulus steroid metabolic process extrinsic apoptotic signaling pathway negative regulation of Wnt signaling pathway skeletal system morphogenesis Wnt signaling pathway positive regulation of extrinsic apoptotic signaling pathway in absence of ligand osteoblast differentiation intrinsic apoptotic signaling pathway by p53 class mediator positive regulation of extrinsic apoptotic signaling pathway positive regulation of transcription by RNA polymerase II apoptotic process negative regulation of transcription by RNA polymerase II transcription by RNA polymerase IISources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez5174180707EnsemblENSG00000186153ENSMUSG00000004637UniProtQ9NZC7Q91WL8RefSeq mRNA NM 001291997NM 016373NM 018560NM 130788NM 130790NM 130791NM 130792NM 130844NM 019573RefSeq protein NP 001278926NP 057457NP 570607NP 062519Location UCSC Chr 16 78 1 79 21 MbChr 8 115 17 116 08 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Interactions 3 References 4 Further readingFunction EditWW 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 2 WW domains and a short chain dehydrogenase reductase domain SRD The highest normal expression of this gene is detected in hormonally regulated tissues such as testis ovary and prostate This expression pattern and the presence of an SRD domain suggest a role for this gene in steroid metabolism The encoded protein is more than 90 identical to the mouse protein which is an essential mediator of tumor necrosis factor alpha induced apoptosis suggesting a similar important role in apoptosis for the human protein In addition there is evidence that this gene behaves as a suppressor of tumor growth Alternative splicing of this gene generates transcript variants that encode different isoforms 8 WWOX is also known as human accelerated region 6 It may therefore have played a key role in differentiating humans from apes 9 Interactions EditWWOX has been shown to interact with P53 and ACK1 10 11 References Edit a b c GRCh38 Ensembl release 89 ENSG00000186153 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000004637 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Bednarek AK Laflin KJ Daniel RL Liao Q Hawkins KA Aldaz CM May 2000 WWOX a novel WW domain containing protein mapping to human chromosome 16q23 3 24 1 a region frequently affected in breast cancer Cancer Res 60 8 2140 5 PMID 10786676 Ried K Finnis M Hobson L Mangelsdorf M Dayan S Nancarrow JK Woollatt E Kremmidiotis G Gardner A Venter D Baker E Richards RI Sep 2000 Common chromosomal fragile site FRA16D sequence identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells Hum Mol Genet 9 11 1651 63 doi 10 1093 hmg 9 11 1651 PMID 10861292 Persson B Kallberg Y Bray JE Bruford E Dellaporta SL Favia AD Duarte RG Jornvall H Kavanagh KL Kedishvili N Kisiela M Maser E Mindnich R Orchard S Penning TM Thornton JM Adamski J Oppermann U Feb 2009 The SDR Short Chain Dehydrogenase Reductase and Related Enzymes Nomenclature Initiative Chem Biol Interact 178 1 3 94 8 doi 10 1016 j cbi 2008 10 040 PMC 2896744 PMID 19027726 a b Entrez Gene WWOX WW domain containing oxidoreductase Pollard KS Salama SR Lambert N Lambot MA Coppens S Pedersen JS Katzman S King B Onodera C Siepel A Kern AD Dehay C Igel H Ares M Vanderhaeghen P Haussler D 2006 08 16 An RNA gene expressed during cortical development evolved rapidly in humans PDF Nature 443 7108 167 72 Bibcode 2006Natur 443 167P doi 10 1038 nature05113 PMID 16915236 S2CID 18107797 supplement Chang NS Pratt N Heath J Schultz L Sleve D Carey GB Zevotek N February 2001 Hyaluronidase induction of a WW domain containing oxidoreductase that enhances tumor necrosis factor cytotoxicity J Biol Chem 276 5 3361 70 doi 10 1074 jbc M007140200 PMID 11058590 Mahajan NP Whang YE Mohler JL Earp HS November 2005 Activated tyrosine kinase Ack1 promotes prostate tumorigenesis role of Ack1 in polyubiquitination of tumor suppressor Wwox Cancer Res 65 22 10514 23 CiteSeerX 10 1 1 322 9333 doi 10 1158 0008 5472 can 05 1127 PMID 16288044 Further reading EditRamos D Aldaz CM 2006 WWOX a Chromosomal Fragile Site Gene and its Role in Cancer New trends in cancer for the 21st century Advances in Experimental Medicine and Biology Vol 587 pp 149 59 doi 10 1007 978 1 4020 5133 3 14 ISBN 978 1 4020 4966 8 PMID 17163164 Chang NS Pratt N Heath J Schultz L Sleve D Carey GB Zevotek N 2001 Hyaluronidase induction of a WW domain containing oxidoreductase that enhances tumor necrosis factor cytotoxicity J Biol Chem 276 5 3361 70 doi 10 1074 jbc M007140200 PMID 11058590 Paige AJ Taylor KJ Taylor C Hillier SG Farrington S Scott D Porteous DJ Smyth JF Gabra H Watson JE 2001 WWOX A candidate tumor suppressor gene involved in multiple tumor types Proc Natl Acad Sci U S A 98 20 11417 22 Bibcode 2001PNAS 9811417P doi 10 1073 pnas 191175898 PMC 58744 PMID 11572989 Bednarek AK Keck Waggoner CL Daniel RL Laflin KJ Bergsagel PL Kiguchi K Brenner AJ Aldaz CM 2001 WWOX the FRA16D gene behaves as a suppressor of tumor growth Cancer Res 61 22 8068 73 PMID 11719429 Kuroki T Trapasso F Shiraishi T Alder H Mimori K Mori M Croce CM 2002 Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma Cancer Res 62 8 2258 60 PMID 11956080 Chang NS Doherty J Ensign A 2003 JNK1 physically interacts with WW domain containing oxidoreductase WOX1 and inhibits WOX1 mediated apoptosis J Biol Chem 278 11 9195 202 doi 10 1074 jbc M208373200 PMID 12514174 Ludes Meyers JH Bednarek AK Popescu NC Bedford M Aldaz CM 2004 WWOX the common chromosomal fragile site FRA16D cancer gene Cytogenet Genome Res 100 1 4 101 10 doi 10 1159 000072844 PMC 4150470 PMID 14526170 Watanabe A Hippo Y Taniguchi H Iwanari H Yashiro M Hirakawa K Kodama T Aburatani H 2004 An opposing view on WWOX protein function as a tumor suppressor Cancer Res 63 24 8629 33 PMID 14695174 Chen ST Chuang JI Wang JP Tsai MS Li H Chang NS 2004 Expression of WW domain containing oxidoreductase WOX1 in the developing murine nervous system Neuroscience 124 4 831 9 doi 10 1016 j neuroscience 2003 12 036 PMID 15026124 S2CID 14784743 Ishii H Mimori K Vecchione A Sutheesophon K Fujiwara T Mori M Furukawa Y 2004 Effect of exogenous E2F 1 on the expression of common chromosome fragile site genes FHIT and WWOX Biochem Biophys Res Commun 316 4 1088 93 doi 10 1016 j bbrc 2004 02 159 PMID 15044096 Ludes Meyers JH Kil H Bednarek AK Drake J Bedford MT Aldaz CM 2004 WWOX binds the specific proline rich ligand PPXY identification of candidate interacting proteins Oncogene 23 29 5049 55 doi 10 1038 sj onc 1207680 PMC 4143251 PMID 15064722 Aqeilan RI Pekarsky Y Herrero JJ Palamarchuk A Letofsky J Druck T Trapasso F Han SY Melino G Huebner K Croce CM 2004 Functional association between Wwox tumor suppressor protein and p73 a p53 homolog Proc Natl Acad Sci U S A 101 13 4401 6 Bibcode 2004PNAS 101 4401A doi 10 1073 pnas 0400805101 PMC 384759 PMID 15070730 Kuroki T Yendamuri S Trapasso F Matsuyama A Aqeilan RI Alder H Rattan S Cesari R Nolli ML Williams NN Mori M Kanematsu T Croce CM 2004 The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis Clin Cancer Res 10 7 2459 65 doi 10 1158 1078 0432 CCR 03 0096 PMID 15073125 Guler G Uner A Guler N Han SY Iliopoulos D Hauck WW McCue P Huebner K 2004 The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma Cancer 100 8 1605 14 doi 10 1002 cncr 20137 PMID 15073846 S2CID 23157412 Sze CI Su M Pugazhenthi S Jambal P Hsu LJ Heath J Schultz L Chang NS 2004 Down regulation of WW domain containing oxidoreductase induces Tau phosphorylation in vitro A potential role in Alzheimer s disease J Biol Chem 279 29 30498 506 doi 10 1074 jbc M401399200 PMID 15126504 Aqeilan RI Kuroki T Pekarsky Y Albagha O Trapasso F Baffa R Huebner K Edmonds P Croce CM 2004 Loss of WWOX expression in gastric carcinoma Clin Cancer Res 10 9 3053 8 doi 10 1158 1078 0432 CCR 03 0594 PMID 15131042 Park SW Ludes Meyers J Zimonjic DB Durkin ME Popescu NC Aldaz CM 2004 Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma Br J Cancer 91 4 753 9 doi 10 1038 sj bjc 6602023 PMC 2364795 PMID 15266310 nbsp This article on a gene on human chromosome 16 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title WWOX amp oldid 1172369587, wikipedia, wiki, book, books, library,
