WWOX Human

The WWOX gene was first identified through shotgun genomic sequencing and analysis of transcripts mapping to a region of chromosome 16 commonly affected by allelic loss in breast cancer . Researchers Bednarek et al. (2000) cloned the gene and named it WWOX due to its structure, which includes two WW domains and a region with high homology to the SRD family of enzymes . The gene was independently identified by Ried et al. (2000) and named FOR (fragile site FRA16D oxidoreductase) .

WWOX is expressed predominantly in hormonally regulated tissues such as the testis, ovary, and prostate . The protein plays a crucial role in various cellular functions, including protein degradation, transcription, and RNA splicing . The presence of WW domains suggests a role in protein-protein interactions, while the SRD domain indicates involvement in steroid metabolism .

WWOX has been shown to be an essential mediator of tumor necrosis factor-alpha-induced apoptosis . It binds directly to the p53 protein, a well-known tumor suppressor, and is involved in p53-mediated apoptosis . The high conservation of WWOX protein between humans and mice (93% identity) supports its significant role in apoptosis . Additionally, WWOX behaves as a potent suppressor of tumor growth, and abnormalities in this gene may contribute to carcinogenesis .

Mutations or inactivation of the WWOX gene have been associated with various human cancers, including breast cancer . Wwox null mice, which lack the WWOX gene, die prematurely, precluding adult tumor analysis . However, aging Wwox-heterozygous mice have been observed to develop a higher incidence of mammary tumors .