WW domain-containing oxidoreductase; fragile site FRA16D oxidoreductase (WWOX, FOR, WOX1)

^[1]^[2]^[3]

Function

putative oxidoreductase
tumor suppressor
role in apoptosis
required for normal bone development (putative)
may function synergistically with TP53/p53 to control genotoxic stress-induced cell death
role in TGFB1 signaling & TGFB1-mediated cell death
role in TNF-mediated cell death (putative)
inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm
phosphorylated upon genotoxic stress
- phosphorylation of Tyr-33 regulates interaction with TP53,TP73 & MAPK8
- phosphorylation may also regulate proapoptotic activity
- phosphorylation by TNK2 is associated with polyubiquitination & degradation
interacts with TP53, TP73/p73 & MAPK8.
interacts with MAPT/TAU, RUNX2 & HYAL2 (putative)
forms a ternary complex with TP53 & MDM2
interacts with ERBB4, LITAF & WBP1
interacts with DVL1, DVL2 & DVL3
interacts with TNK2
interacts with TMEM207
may interact with COTE1/C1orf2 (FAM189B) & SCOTIN

belongs to the short-chain dehydrogenases/reductases (SDR) family
contains 2 WW domains WW 1 domain mediates interaction with TP53, & probably TP73, TFAP2C, LITAF & WBP1

overexpressed in cancer cell lines
isoforms 5 & 6 may only be expressed in tumor cell lines
defects in WWOX may be involved in several cancer types
alteration of WWOX expression & expression of some WWOX isoforms is associated with cancers; however, it is unclear if alteration of WWOX is directly implicated in cancerogenesis or if it corresponds to a secondary effect
defects in WWOX may be involved in esophageal cancer (esophageal squamous cell carcinoma)
defects in WWOX may be the cause of
- spinocerebellar ataxia, autosomal recessive 12 (SACR12)
- early infantile epileptic encephalopathy 28 (EIEE28)

WWOX gene spans the 2nd most common chromosomal fragile site (FRA16D) which is frequently altered in cancers