WWOX Induces MEK2-Mediated Cell Death in a p53 Independent Manner

摘要

WW domain-containing oxidoreductase WWOX that contains two WW domains in the N-terminus, which are involved in protein-protein interactions, and an alcohol dehydrogenase (ADH) domain is a putative tumor suppressor and a proapoptotic protein. It has been reported that WWOX gene is located at the common fragile site FRA16D in chromosome 16q23.3-24.1 and its expression is down-regulated in various cancer types. Furthermore, aberrantly spliced WWOX mRNA forms that were not detected in normal cells were detected in cancer cell lines and primary breast tumors.3 In addition, loss of WWOX expression resulted in resistance to apoptosis induced by tumor necrosis factor, staurosporine, UV, and p53 overexpression whereas overexpressed WWOX promoted apoptosis synergistically with p53.