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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''WW domain-containing oxidoreductase''' is an [[enzyme]] that in humans is encoded by the ''WWOX'' [[gene]].<ref name="pmid10786676">{{cite journal | vauthors = Bednarek AK, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM | title = WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer | journal = Cancer Res | volume = 60 | issue = 8 | pages = 2140–5 | date = May 2000 | pmid = 10786676 | pmc =  | doi =  }}</ref><ref name="pmid10861292">{{cite journal | vauthors = Ried K, Finnis M, Hobson L, Mangelsdorf M, Dayan S, Nancarrow JK, Woollatt E, Kremmidiotis G, Gardner A, Venter D, Baker E, Richards RI | title = Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells | journal = Hum Mol Genet | volume = 9 | issue = 11 | pages = 1651–63 | date = Sep 2000 | pmid = 10861292 | pmc =  | doi = 10.1093/hmg/9.11.1651 }}</ref><ref name="pmid19027726">{{cite journal | vauthors = 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 | title = The SDR (Short-Chain Dehydrogenase/Reductase and Related Enzymes) Nomenclature Initiative | journal = Chem Biol Interact | volume = 178 | issue = 1–3 | pages = 94–8 | date = Feb 2009 | pmid = 19027726 | pmc = 2896744 | doi = 10.1016/j.cbi.2008.10.040 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: WWOX WW domain containing oxidoreductase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51741| accessdate = }}</ref>
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| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_WWOX_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1wmv.
| PDB = {{PDB2|1wmv}}
| Name = WW domain containing oxidoreductase
| HGNCid = 12799
| Symbol = WWOX
| AltSymbols =; FRA16D; D16S432E; FOR; HHCMA56; PRO0128; WOX1; WWOX v8
| OMIM = 605131
| ECnumber = 
| Homologene = 56334
| MGIid = 1931237
| GeneAtlas_image1 = PBB_GE_WWOX_221147_x_at_tn.png
| Function = {{GNF_GO|id=GO:0016491 |text = oxidoreductase activity}} {{GNF_GO|id=GO:0046983 |text = protein dimerization activity}} {{GNF_GO|id=GO:0050662 |text = coenzyme binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005739 |text = mitochondrion}}
| Process = {{GNF_GO|id=GO:0006118 |text = electron transport}} {{GNF_GO|id=GO:0007049 |text = cell cycle}} {{GNF_GO|id=GO:0008152 |text = metabolic process}} {{GNF_GO|id=GO:0008202 |text = steroid metabolic process}} {{GNF_GO|id=GO:0045786 |text = negative regulation of progression through cell cycle}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 51741
    | Hs_Ensembl = ENSG00000186153
    | Hs_RefseqProtein = NP_057457
    | Hs_RefseqmRNA = NM_016373
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 16
    | Hs_GenLoc_start = 76691177
    | Hs_GenLoc_end = 77803532
    | Hs_Uniprot = 
    | Mm_EntrezGene = 80707
    | Mm_Ensembl = ENSMUSG00000004637
    | Mm_RefseqmRNA = NM_019573
    | Mm_RefseqProtein = NP_062519
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 8
    | Mm_GenLoc_start = 117325749
    | Mm_GenLoc_end = 118237803
    | Mm_Uniprot = Q91WL8
  }}
}}
'''WW domain containing oxidoreductase''', also known as '''WWOX''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: WWOX WW domain containing oxidoreductase| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51741| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
[[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.<ref name="entrez" />
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: WWOX WW domain containing oxidoreductase| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51741| accessdate = }}</ref>
}}


==References==
WWOX is also known as [[human accelerated regions|human accelerated region]] 6.  It may, therefore, have played a key role in differentiating humans from apes.<ref name="Pollard2006">{{cite journal | vauthors = 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 | title = An RNA gene expressed during cortical development evolved rapidly in humans | journal = Nature | volume = 443 | issue = 7108 | pages = 167–72 | date = 2006-08-16 | pmid = 16915236 | doi = 10.1038/nature05113 }} [http://www.nature.com/nature/journal/v443/n7108/extref/nature05113-s1.doc supplement]</ref>
{{reflist|2}}
 
==Further reading==
== Interactions ==
 
WWOX has been shown to [[Protein-protein interaction|interact]] with [[P53]] and [[TNK2|ACK1]].<ref name="pmid11058590">{{cite journal | vauthors = Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N | title = Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity | journal = J. Biol. Chem. | volume = 276 | issue = 5 | pages = 3361–70 | date = February 2001 | pmid = 11058590 | doi = 10.1074/jbc.M007140200 }}</ref><ref name="pmid16288044">{{cite journal | vauthors = Mahajan NP, Whang YE, Mohler JL, Earp HS | title = Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. | journal = Cancer Res. | volume = 65 | issue = 22 | pages = 10514–23 | date = November 2005 | pmid = 16288044 | doi = 10.1158/0008-5472.can-05-1127 | citeseerx = 10.1.1.322.9333 }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{Cite book | vauthors = Ramos D, Aldaz CM | title = WWOX, a chromosomal fragile site gene and its role in cancer | journal = Adv. Exp. Med. Biol. | volume = 587 | issue =  | pages = 149–59 | year = 2007 | pmid = 17163164 | doi = 10.1007/978-1-4020-5133-3_14 | series = Advances in Experimental Medicine and Biology | isbn = 978-1-4020-4966-8 }}
| citations =
* {{cite journal | vauthors = Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N | title = Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity | journal = J. Biol. Chem. | volume = 276 | issue = 5 | pages = 3361–70 | year = 2001 | pmid = 11058590 | doi = 10.1074/jbc.M007140200 }}
*{{cite journal  | author=Ramos D, Aldaz CM |title=WWOX, a chromosomal fragile site gene and its role in cancer. |journal=Adv. Exp. Med. Biol. |volume=587 |issue=  |pages= 149-59 |year= 2007 |pmid= 17163164 |doi= }}
* {{cite journal | vauthors = Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, Scott D, Porteous DJ, Smyth JF, Gabra H, Watson JE | title = WWOX: A candidate tumor suppressor gene involved in multiple tumor types | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 20 | pages = 11417–22 | year = 2001 | pmid = 11572989 | pmc = 58744 | doi = 10.1073/pnas.191175898 }}
*{{cite journal | author=Bednarek AK, Laflin KJ, Daniel RL, ''et al.'' |title=WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer. |journal=Cancer Res. |volume=60 |issue= 8 |pages= 2140-5 |year= 2000 |pmid= 10786676 |doi= }}
* {{cite journal | vauthors = Bednarek AK, Keck-Waggoner CL, Daniel RL, Laflin KJ, Bergsagel PL, Kiguchi K, Brenner AJ, Aldaz CM | title = WWOX, the FRA16D gene, behaves as a suppressor of tumor growth | journal = Cancer Res. | volume = 61 | issue = 22 | pages = 8068–73 | year = 2001 | pmid = 11719429 | doi = }}
*{{cite journal | author=Ried K, Finnis M, Hobson L, ''et al.'' |title=Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells. |journal=Hum. Mol. Genet. |volume=9 |issue= 11 |pages= 1651-63 |year= 2000 |pmid= 10861292 |doi= }}
* {{cite journal | vauthors = Kuroki T, Trapasso F, Shiraishi T, Alder H, Mimori K, Mori M, Croce CM | title = Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma | journal = Cancer Res. | volume = 62 | issue = 8 | pages = 2258–60 | year = 2002 | pmid = 11956080 | doi = }}
*{{cite journal | author=Chang NS, Pratt N, Heath J, ''et al.'' |title=Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity. |journal=J. Biol. Chem. |volume=276 |issue= 5 |pages= 3361-70 |year= 2001 |pmid= 11058590 |doi= 10.1074/jbc.M007140200 }}
* {{cite journal | vauthors = Chang NS, Doherty J, Ensign A | title = JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis | journal = J. Biol. Chem. | volume = 278 | issue = 11 | pages = 9195–202 | year = 2003 | pmid = 12514174 | doi = 10.1074/jbc.M208373200 }}
*{{cite journal | author=Paige AJ, Taylor KJ, Taylor C, ''et al.'' |title=WWOX: a candidate tumor suppressor gene involved in multiple tumor types. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 20 |pages= 11417-22 |year= 2001 |pmid= 11572989 |doi= 10.1073/pnas.191175898 }}
* {{cite journal | vauthors = Ludes-Meyers JH, Bednarek AK, Popescu NC, Bedford M, Aldaz CM | title = WWOX, the common chromosomal fragile site, FRA16D, cancer gene | journal = Cytogenet. Genome Res. | volume = 100 | issue = 1–4 | pages = 101–10 | year = 2004 | pmid = 14526170 | pmc = 4150470 | doi = 10.1159/000072844 }}
*{{cite journal | author=Bednarek AK, Keck-Waggoner CL, Daniel RL, ''et al.'' |title=WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. |journal=Cancer Res. |volume=61 |issue= 22 |pages= 8068-73 |year= 2001 |pmid= 11719429 |doi= }}
* {{cite journal | vauthors = Watanabe A, Hippo Y, Taniguchi H, Iwanari H, Yashiro M, Hirakawa K, Kodama T, Aburatani H | title = An opposing view on WWOX protein function as a tumor suppressor | journal = Cancer Res. | volume = 63 | issue = 24 | pages = 8629–33 | year = 2004 | pmid = 14695174 | doi = }}
*{{cite journal | author=Kuroki T, Trapasso F, Shiraishi T, ''et al.'' |title=Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma. |journal=Cancer Res. |volume=62 |issue= 8 |pages= 2258-60 |year= 2002 |pmid= 11956080 |doi= }}
* {{cite journal | vauthors = Chen ST, Chuang JI, Wang JP, Tsai MS, Li H, Chang NS | title = Expression of WW domain-containing oxidoreductase WOX1 in the developing murine nervous system | journal = Neuroscience | volume = 124 | issue = 4 | pages = 831–9 | year = 2004 | pmid = 15026124 | doi = 10.1016/j.neuroscience.2003.12.036 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Ishii H, Mimori K, Vecchione A, Sutheesophon K, Fujiwara T, Mori M, Furukawa Y | title = Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX | journal = Biochem. Biophys. Res. Commun. | volume = 316 | issue = 4 | pages = 1088–93 | year = 2004 | pmid = 15044096 | doi = 10.1016/j.bbrc.2004.02.159 }}
*{{cite journal | author=Chang NS, Doherty J, Ensign A |title=JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis. |journal=J. Biol. Chem. |volume=278 |issue= 11 |pages= 9195-202 |year= 2003 |pmid= 12514174 |doi= 10.1074/jbc.M208373200 }}
* {{cite journal | vauthors = Ludes-Meyers JH, Kil H, Bednarek AK, Drake J, Bedford MT, Aldaz CM | title = WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins | journal = Oncogene | volume = 23 | issue = 29 | pages = 5049–55 | year = 2004 | pmid = 15064722 | doi = 10.1038/sj.onc.1207680 | pmc = 4143251 }}
*{{cite journal | author=Ludes-Meyers JH, Bednarek AK, Popescu NC, ''et al.'' |title=WWOX, the common chromosomal fragile site, FRA16D, cancer gene. |journal=Cytogenet. Genome Res. |volume=100 |issue= 1-4 |pages= 101-10 |year= 2004 |pmid= 14526170 |doi= 10.1159/000072844 }}
* {{cite journal | vauthors = Aqeilan RI, Pekarsky Y, Herrero JJ, Palamarchuk A, Letofsky J, Druck T, Trapasso F, Han SY, Melino G, Huebner K, Croce CM | title = Functional association between Wwox tumor suppressor protein and p73, a p53 homolog | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 101 | issue = 13 | pages = 4401–6 | year = 2004 | pmid = 15070730 | pmc = 384759 | doi = 10.1073/pnas.0400805101 }}
*{{cite journal | author=Watanabe A, Hippo Y, Taniguchi H, ''et al.'' |title=An opposing view on WWOX protein function as a tumor suppressor. |journal=Cancer Res. |volume=63 |issue= 24 |pages= 8629-33 |year= 2004 |pmid= 14695174 |doi= }}
* {{cite journal | vauthors = 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 | title = The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis | journal = Clin. Cancer Res. | volume = 10 | issue = 7 | pages = 2459–65 | year = 2004 | pmid = 15073125 | doi = 10.1158/1078-0432.CCR-03-0096 }}
*{{cite journal | author=Chen ST, Chuang JI, Wang JP, ''et al.'' |title=Expression of WW domain-containing oxidoreductase WOX1 in the developing murine nervous system. |journal=Neuroscience |volume=124 |issue= 4 |pages= 831-9 |year= 2004 |pmid= 15026124 |doi= 10.1016/j.neuroscience.2003.12.036 }}
* {{cite journal | vauthors = Guler G, Uner A, Guler N, Han SY, Iliopoulos D, Hauck WW, McCue P, Huebner K | title = The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma | journal = Cancer | volume = 100 | issue = 8 | pages = 1605–14 | year = 2004 | pmid = 15073846 | doi = 10.1002/cncr.20137 }}
*{{cite journal | author=Ishii H, Mimori K, Vecchione A, ''et al.'' |title=Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX. |journal=Biochem. Biophys. Res. Commun. |volume=316 |issue= 4 |pages= 1088-93 |year= 2004 |pmid= 15044096 |doi= 10.1016/j.bbrc.2004.02.159 }}
* {{cite journal | vauthors = Sze CI, Su M, Pugazhenthi S, Jambal P, Hsu LJ, Heath J, Schultz L, Chang NS | title = Down-regulation of WW domain-containing oxidoreductase induces Tau phosphorylation in vitro. A potential role in Alzheimer's disease | journal = J. Biol. Chem. | volume = 279 | issue = 29 | pages = 30498–506 | year = 2004 | pmid = 15126504 | doi = 10.1074/jbc.M401399200 }}
*{{cite journal | author=Ludes-Meyers JH, Kil H, Bednarek AK, ''et al.'' |title=WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins. |journal=Oncogene |volume=23 |issue= 29 |pages= 5049-55 |year= 2004 |pmid= 15064722 |doi= 10.1038/sj.onc.1207680 }}
* {{cite journal | vauthors = Aqeilan RI, Kuroki T, Pekarsky Y, Albagha O, Trapasso F, Baffa R, Huebner K, Edmonds P, Croce CM | title = Loss of WWOX expression in gastric carcinoma | journal = Clin. Cancer Res. | volume = 10 | issue = 9 | pages = 3053–8 | year = 2004 | pmid = 15131042 | doi = 10.1158/1078-0432.CCR-03-0594 }}
*{{cite journal | author=Aqeilan RI, Pekarsky Y, Herrero JJ, ''et al.'' |title=Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 13 |pages= 4401-6 |year= 2004 |pmid= 15070730 |doi= 10.1073/pnas.0400805101 }}
* {{cite journal | vauthors = Park SW, Ludes-Meyers J, Zimonjic DB, Durkin ME, Popescu NC, Aldaz CM | title = Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma | journal = Br. J. Cancer | volume = 91 | issue = 4 | pages = 753–9 | year = 2004 | pmid = 15266310 | pmc = 2364795 | doi = 10.1038/sj.bjc.6602023 }}
*{{cite journal | author=Kuroki T, Yendamuri S, Trapasso F, ''et al.'' |title=The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis. |journal=Clin. Cancer Res. |volume=10 |issue= 7 |pages= 2459-65 |year= 2004 |pmid= 15073125 |doi= }}
*{{cite journal | author=Guler G, Uner A, Guler N, ''et al.'' |title=The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma. |journal=Cancer |volume=100 |issue= 8 |pages= 1605-14 |year= 2004 |pmid= 15073846 |doi= 10.1002/cncr.20137 }}
*{{cite journal  | author=Sze CI, Su M, Pugazhenthi S, ''et al.'' |title=Down-regulation of WW domain-containing oxidoreductase induces Tau phosphorylation in vitro. A potential role in Alzheimer's disease. |journal=J. Biol. Chem. |volume=279 |issue= 29 |pages= 30498-506 |year= 2004 |pmid= 15126504 |doi= 10.1074/jbc.M401399200 }}
*{{cite journal  | author=Aqeilan RI, Kuroki T, Pekarsky Y, ''et al.'' |title=Loss of WWOX expression in gastric carcinoma. |journal=Clin. Cancer Res. |volume=10 |issue= 9 |pages= 3053-8 |year= 2004 |pmid= 15131042 |doi=  }}
*{{cite journal  | author=Park SW, Ludes-Meyers J, Zimonjic DB, ''et al.'' |title=Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma. |journal=Br. J. Cancer |volume=91 |issue= 4 |pages= 753-9 |year= 2004 |pmid= 15266310 |doi= 10.1038/sj.bjc.6602023 }}
}}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=51741}}


{{protein-stub}}
{{gene-16-stub}}

Latest revision as of 09:24, 10 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

WW domain-containing oxidoreductase is an enzyme that in humans is encoded by the WWOX gene.[1][2][3][4]

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 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.[4]

WWOX is also known as human accelerated region 6. It may, therefore, have played a key role in differentiating humans from apes.[5]

Interactions

WWOX has been shown to interact with P53 and ACK1.[6][7]

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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. PMC 2896744. PMID 19027726.
  4. ↑ 4.0 4.1 "Entrez Gene: WWOX WW domain containing oxidoreductase".
  5. ↑ 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". Nature. 443 (7108): 167–72. doi:10.1038/nature05113. PMID 16915236. supplement
  6. ↑ 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.
  7. ↑ 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


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