1wmv

Structural highlights

Disease

[WWOX_HUMAN] Note=Defects in WWOX may be involved in several cancer types. The gene spans the second most common chromosomal fragile site (FRA16D) which is frequently altered in cancers. Alteration of the expression and expression of some isoforms is associated with cancers. However, it is still unclear if alteration of WWOX is directly implicated in cancerogenesis or if it corresponds to a secondary effect.^{[1] [2] [3] [4] [5]} Defects in WWOX may be a cause of esophageal cancer (ESCR) [MIM:133239].^{[6] [7] [8] [9] [10]}

Function

[WWOX_HUMAN] Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm.^{[11] [12] [13] [14] [15] [16] [17]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, Scott D, Porteous DJ, Smyth JF, Gabra H, Watson JE. WWOX: a candidate tumor suppressor gene involved in multiple tumor types. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11417-22. PMID:11572989 doi:10.1073/pnas.191175898
2. ↑ Park SW, Ludes-Meyers J, Zimonjic DB, Durkin ME, Popescu NC, Aldaz CM. Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma. Br J Cancer. 2004 Aug 16;91(4):753-9. PMID:15266310 doi:10.1038/sj.bjc.6602023
3. ↑ 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. The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis. Clin Cancer Res. 2004 Apr 1;10(7):2459-65. PMID:15073125
4. ↑ Aqeilan RI, Kuroki T, Pekarsky Y, Albagha O, Trapasso F, Baffa R, Huebner K, Edmonds P, Croce CM. Loss of WWOX expression in gastric carcinoma. Clin Cancer Res. 2004 May 1;10(9):3053-8. PMID:15131042
5. ↑ Fabbri M, Iliopoulos D, Trapasso F, Aqeilan RI, Cimmino A, Zanesi N, Yendamuri S, Han SY, Amadori D, Huebner K, Croce CM. WWOX gene restoration prevents lung cancer growth in vitro and in vivo. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15611-6. Epub 2005 Oct 13. PMID:16223882 doi:0505485102
6. ↑ Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, Scott D, Porteous DJ, Smyth JF, Gabra H, Watson JE. WWOX: a candidate tumor suppressor gene involved in multiple tumor types. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11417-22. PMID:11572989 doi:10.1073/pnas.191175898
7. ↑ Park SW, Ludes-Meyers J, Zimonjic DB, Durkin ME, Popescu NC, Aldaz CM. Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma. Br J Cancer. 2004 Aug 16;91(4):753-9. PMID:15266310 doi:10.1038/sj.bjc.6602023
8. ↑ 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. The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis. Clin Cancer Res. 2004 Apr 1;10(7):2459-65. PMID:15073125
9. ↑ Aqeilan RI, Kuroki T, Pekarsky Y, Albagha O, Trapasso F, Baffa R, Huebner K, Edmonds P, Croce CM. Loss of WWOX expression in gastric carcinoma. Clin Cancer Res. 2004 May 1;10(9):3053-8. PMID:15131042
10. ↑ Fabbri M, Iliopoulos D, Trapasso F, Aqeilan RI, Cimmino A, Zanesi N, Yendamuri S, Han SY, Amadori D, Huebner K, Croce CM. WWOX gene restoration prevents lung cancer growth in vitro and in vivo. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15611-6. Epub 2005 Oct 13. PMID:16223882 doi:0505485102
11. ↑ Bednarek AK, Keck-Waggoner CL, Daniel RL, Laflin KJ, Bergsagel PL, Kiguchi K, Brenner AJ, Aldaz CM. WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. Cancer Res. 2001 Nov 15;61(22):8068-73. PMID:11719429
12. ↑ Aqeilan RI, Palamarchuk A, Weigel RJ, Herrero JJ, Pekarsky Y, Croce CM. Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor. Cancer Res. 2004 Nov 15;64(22):8256-61. PMID:15548692 doi:10.1158/0008-5472.CAN-04-2055
13. ↑ Aqeilan RI, Pekarsky Y, Herrero JJ, Palamarchuk A, Letofsky J, Druck T, Trapasso F, Han SY, Melino G, Huebner K, Croce CM. Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4401-6. PMID:15070730 doi:10.1073/pnas.0400805101
14. ↑ Aqeilan RI, Donati V, Palamarchuk A, Trapasso F, Kaou M, Pekarsky Y, Sudol M, Croce CM. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res. 2005 Aug 1;65(15):6764-72. PMID:16061658 doi:10.1158/0008-5472.CAN-05-1150
15. ↑ Chang NS, Doherty J, Ensign A, Schultz L, Hsu LJ, Hong Q. WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53. J Biol Chem. 2005 Dec 30;280(52):43100-8. Epub 2005 Oct 11. PMID:16219768 doi:M505590200
16. ↑ Hsu LJ, Schultz L, Hong Q, Van Moer K, Heath J, Li MY, Lai FJ, Lin SR, Lee MH, Lo CP, Lin YS, Chen ST, Chang NS. Transforming growth factor beta1 signaling via interaction with cell surface Hyal-2 and recruitment of WWOX/WOX1. J Biol Chem. 2009 Jun 5;284(23):16049-59. doi: 10.1074/jbc.M806688200. Epub 2009 , Apr 14. PMID:19366691 doi:10.1074/jbc.M806688200
17. ↑ Bouteille N, Driouch K, Hage PE, Sin S, Formstecher E, Camonis J, Lidereau R, Lallemand F. Inhibition of the Wnt/beta-catenin pathway by the WWOX tumor suppressor protein. Oncogene. 2009 Jul 16;28(28):2569-80. doi: 10.1038/onc.2009.120. Epub 2009 May, 25. PMID:19465938 doi:10.1038/onc.2009.120