disease:Defects in WWOX may be involved in esophageal squamous cell carcinoma (ESCC) [MIM:133239].,disease: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.,domain:The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1.,function:Probable oxidoreductase, which acts as a tumor suppressor and plays a role in apoptosis. May function synergistically with TP53/p53 to control genotoxic stress-induced cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death.,PTM:Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33 regulates interaction with TP53, TP73 and MAPK8. May also regulate proapoptotic activity.,similarity:Belongs to the short-chain dehydrogenases/reductases (SDR) family.,similarity:Contains 2 WW domains.,subcellular location:Partially localizes to the mitochondria. Translocates to the nucleus upon genotoxic stress or TNF stimulation (By similarity). Isoform 5 and isoform 6 may localize in the nucleus.,subunit:Interacts with TP53, TP73/p73 and MAPK8. Interacts with MAPT/TAU (By similarity). Forms a ternary complex with TP53 and MDM2. Interacts with ERBB4, LITAF and WBP1. May interact with COTE1/C1orf2 and SCOTIN.,tissue specificity:Widely expressed. Strongly expressed in testis, prostate, and ovary. Overexpressed in cancer cell lines. Isoform 5 and isoform 6 may only be expressed in tumor cell lines.,