The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

WWOX  -  WW domain containing oxidoreductase

Homo sapiens

Synonyms: D16S432E, FOR, FRA16D, Fragile site FRA16D oxidoreductase, HHCMA56, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of WWOX


High impact information on WWOX


Biological context of WWOX

  • The FOR (WWOX) gene spans FRA16D and encodes a partner of p53 that also has a role in apoptosis [9].
  • Transcripts missing WWOX exons were detected in 7 primary tumors (7 of 27; 25.9%) and 5 of 8 cell lines [1].
  • In addition, loss of heterozygosity at the WWOX locus was observed in 10 primary tumors (10 of 27; 37.0%) [1].
  • WW domain-containing oxidoreductase WOX1, also named WWOX or FOR, undergoes Tyr33 phosphorylation at its first N-terminal WW domain and subsequent nuclear translocation in response to sex steroid hormones and stress stimuli [10].
  • Differential patterns of WWOX and FHIT methylation were observed in neoplastic vs adjacent non-neoplastic tissues, suggesting that targeted MSP amplification could be useful in following treatment or prevention protocols [2].

Anatomical context of WWOX

  • Previously untested 53 cancer cell lines were screened for deletions within the FOR/WWOX gene [9].
  • Coexpression of WWOX and ErbB-4 in HeLa cells followed by treatment with TPA results in the retention of ErbB-4 in the cytoplasm [11].
  • The results from our study indicate that WWOX is preferentially highly expressed in secretory epithelial cells of reproductive, endocrine and exocrine organs, as well as in ductal epithelial cells from specific segments of the urinary system [12].
  • Due to the potential role of WWOX in sex-steroid metabolism, whole sections from hormonally regulated organs like breast, ovaries, testes and prostate were also analyzed [12].
  • Interestingly, we also observed significant WWOX protein expression in various cell types of neural origin including neurons, ependymal cells and astrocytes [12].

Associations of WWOX with chemical compounds

  • Methylation analysis showed that site-specific promoter hypermethylation was detected in 2 cell lines (22%) and treatment with the demethylating agent 5-aza-2'-deoxycytidine demonstrated an increase in the expression of WWOX [13].
  • Our biochemical study reveals that ezrin directly binds to the first WW domain of WWOX via its C-terminal tyrosine-containing polyproline sequence (470)PPPPPPVY(477) [14].
  • Estrogen and androgen stimulate phosphorylation and nuclear translocation of WWOX, although binding of WWOX to these sex hormones is unknown [15].
  • Conformationally altered hyaluronan restricts complement classical pathway activation by binding to C1q, C1r, C1s, C2, C5 and C9, and suppresses WOX1 expression in prostate DU145 cells [16].

Physical interactions of WWOX


Regulatory relationships of WWOX

  • In addition, our results show that interaction of WWOX and ErbB-4 suppresses transcriptional coactivation of CTF by YAP in a dose-dependent manner [11].
  • WOX1 induced apoptosis synergistically with p53 [17].

Other interactions of WWOX

  • Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer [2].
  • Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX [19].
  • Aberration or absence of WWOX expression recently was detected in primary hematopoietic malignancies [20].
  • In summary, our data indicate that WWOX antagonizes the function of YAP by competing for interaction with ErbB-4 and other targets and thus affect its transcriptional activity [11].
  • Mutational analyses further demonstrate that tyrosine(477) is essential for the ezrin-WWOX interaction [14].

Analytical, diagnostic and therapeutic context of WWOX


  1. WW domain containing oxidoreductase gene expression is altered in non-small cell lung cancer. Yendamuri, S., Kuroki, T., Trapasso, F., Henry, A.C., Dumon, K.R., Huebner, K., Williams, N.N., Kaiser, L.R., Croce, C.M. Cancer Res. (2003) [Pubmed]
  2. Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer. Iliopoulos, D., Guler, G., Han, S.Y., Johnston, D., Druck, T., McCorkell, K.A., Palazzo, J., McCue, P.A., Baffa, R., Huebner, K. Oncogene (2005) [Pubmed]
  3. Loss of WWOX expression in gastric carcinoma. Aqeilan, R.I., Kuroki, T., Pekarsky, Y., Albagha, O., Trapasso, F., Baffa, R., Huebner, K., Edmonds, P., Croce, C.M. Clin. Cancer Res. (2004) [Pubmed]
  4. A novel approach to simultaneously scan genes at fragile sites. Willem, P., Brown, J., Schouten, J. BMC Cancer (2006) [Pubmed]
  5. Expression of FRA16D/WWOX and FRA3B/FHIT genes in hematopoietic malignancies. Ishii, H., Vecchione, A., Furukawa, Y., Sutheesophon, K., Han, S.Y., Druck, T., Kuroki, T., Trapasso, F., Nishimura, M., Saito, Y., Ozawa, K., Croce, C.M., Huebner, K., Furukawa, Y. Mol. Cancer Res. (2003) [Pubmed]
  6. WWOX expression in different histologic types and subtypes of non-small cell lung cancer. Donati, V., Fontanini, G., Dell'Omodarme, M., Prati, M.C., Nuti, S., Lucchi, M., Mussi, A., Fabbri, M., Basolo, F., Croce, C.M., Aqeilan, R.I. Clin. Cancer Res. (2007) [Pubmed]
  7. WWOX gene restoration prevents lung cancer growth in vitro and in vivo. Fabbri, M., Iliopoulos, D., Trapasso, F., Aqeilan, R.I., Cimmino, A., Zanesi, N., Yendamuri, S., Han, S.Y., Amadori, D., Huebner, K., Croce, C.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. WWOX: a candidate tumor suppressor gene involved in multiple tumor types. Paige, A.J., Taylor, K.J., Taylor, C., Hillier, S.G., Farrington, S., Scott, D., Porteous, D.J., Smyth, J.F., Gabra, H., Watson, J.E. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  9. Common chromosomal fragile site FRA16D mutation in cancer cells. Finnis, M., Dayan, S., Hobson, L., Chenevix-Trench, G., Friend, K., Ried, K., Venter, D., Woollatt, E., Baker, E., Richards, R.I. Hum. Mol. Genet. (2005) [Pubmed]
  10. 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. Chang, N.S., Doherty, J., Ensign, A., Schultz, L., Hsu, L.J., Hong, Q. J. Biol. Chem. (2005) [Pubmed]
  11. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Aqeilan, R.I., Donati, V., Palamarchuk, A., Trapasso, F., Kaou, M., Pekarsky, Y., Sudol, M., Croce, C.M. Cancer Res. (2005) [Pubmed]
  12. WWOX protein expression in normal human tissues. Nunez, M.I., Ludes-Meyers, J., Aldaz, C.M. J. Mol. Histol. (2006) [Pubmed]
  13. The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis. Kuroki, T., Yendamuri, S., Trapasso, F., Matsuyama, A., Aqeilan, R.I., Alder, H., Rattan, S., Cesari, R., Nolli, M.L., Williams, N.N., Mori, M., Kanematsu, T., Croce, C.M. Clin. Cancer Res. (2004) [Pubmed]
  14. PKA-mediated protein phosphorylation regulates ezrin-WWOX interaction. Jin, C., Ge, L., Ding, X., Chen, Y., Zhu, H., Ward, T., Wu, F., Cao, X., Wang, Q., Yao, X. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  15. WW domain-containing oxidoreductase: a candidate tumor suppressor. Chang, N.S., Hsu, L.J., Lin, Y.S., Lai, F.J., Sheu, H.M. Trends in molecular medicine (2007) [Pubmed]
  16. Conformationally altered hyaluronan restricts complement classical pathway activation by binding to C1q, C1r, C1s, C2, C5 and C9, and suppresses WOX1 expression in prostate DU145 cells. Hong, Q., Kuo, E., Schultz, L., Boackle, R.J., Chang, N.S. Int. J. Mol. Med. (2007) [Pubmed]
  17. Molecular mechanisms underlying WOX1 activation during apoptotic and stress responses. Chang, N.S., Doherty, J., Ensign, A., Lewis, J., Heath, J., Schultz, L., Chen, S.T., Oppermann, U. Biochem. Pharmacol. (2003) [Pubmed]
  18. WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins. Ludes-Meyers, J.H., Kil, H., Bednarek, A.K., Drake, J., Bedford, M.T., Aldaz, C.M. Oncogene (2004) [Pubmed]
  19. Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX. Ishii, H., Mimori, K., Vecchione, A., Sutheesophon, K., Fujiwara, T., Mori, M., Furukawa, Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  20. Alterations of common chromosome fragile sites in hematopoietic malignancies. Ishii, H., Furukawa, Y. Int. J. Hematol. (2004) [Pubmed]
  21. WWOX, the common chromosomal fragile site, FRA16D, cancer gene. Ludes-Meyers, J.H., Bednarek, A.K., Popescu, N.C., Bedford, M., Aldaz, C.M. Cytogenet. Genome Res. (2003) [Pubmed]
  22. Identification of homozygous deletions at chromosome 16q23 in aflatoxin B1 exposed hepatocellular carcinoma. Yakicier, M.C., Legoix, P., Vaury, C., Gressin, L., Tubacher, E., Capron, F., Bayer, J., Degott, C., Balabaud, C., Zucman-Rossi, J. Oncogene (2001) [Pubmed]
WikiGenes - Universities