Pleiotropic Functions of Tumor Suppressor WWOX in Normal and Cancer Cells.
WW domain-containing oxidoreductase (WWOX), originally marked as a likely tumor suppressor gene, has over the years become recognized for its role in a much wider range of cellular activities. Phenotypic effects displayed in animal studies, along with resolution of WWOX's architecture, fold, and binding partners, point to the protein's multifaceted biological functions. Results from a series of complementary experiments seem to indicate WWOX's involvement in metabolic regulation. More recently, clinical studies involving cases of severe encephalopathy suggest that WWOX also plays a part in controlling CNS development, further expanding our understanding of the breadth and complexity of WWOX behavior. Here we present a short overview of the various approaches taken to study this dynamic gene, emphasizing the most recent findings regarding WWOX's metabolic- and CNS-associated functions and their underlying molecular basis.
From the Departments of Immunology & Cancer Research and.
Muhannad
M
Abu-Remaileh
Microbiology & Molecular Genetics, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel 91120.
Emma
E
Joy-Dodson
Microbiology & Molecular Genetics, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel 91120.
Ora
O
Schueler-Furman
From the Departments of Immunology & Cancer Research and ramiaq@mail.huji.ac.il.
Rami I
RI
Aqeilan
D000818:Animals; D002490:Central Nervous System / Q000201:enzymology*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases
SDR domain; WW domain; WWOX; animal model; animal models; cell metabolism; central nervous system (CNS); common fragile site; epilepsy; protein-protein interaction; tumor suppressor; tumor suppressor gene