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.
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.
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. Defects in WWOX may be a cause of esophageal cancer (ESCR) [MIM:133239].
Belongs to the short-chain dehydrogenases/reductases (SDR) family. Contains 2 WW domains.
The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1.
Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33 regulates interaction with TP53, TP73 and MAPK8. May also regulate proapoptotic activity. Phosphorylation by TNK2 is associated with polyubiquitination and degradation. Ubiquitinated when phosphorylated by TNK2, leading to its degradation.
Cytoplasm. Nucleus. Mitochondrion. Golgi apparatus. Partially localizes to the mitochondria. Translocates to the nucleus upon genotoxic stress or TNF stimulation (By similarity). Translocates to the nucleus in response to TGFB1. Isoform 5 and isoform 6 may localize in the nucleus.