WWOX gene and gene product: tumor suppression through specific protein interactions.
The WWOX gene, an archetypal fragile gene, encompasses a chromosomal fragile site at 16q23.2, and encodes the approximately 46-kDa Wwox protein, with WW domains that interact with a growing list of interesting proteins. If the function of a protein is defined by the company it keeps, then Wwox is involved in numerous important signal pathways for bone and germ-cell development, cellular and animal growth and death, transcriptional control and suppression of cancer development. Because alterations to genes at fragile sites are exquisitely sensitive to replication stress-induced DNA damage, there has been an ongoing scientific discussion questioning whether such gene expression alterations provide a selective advantage for clonal expansion of neoplastic cells, and a parallel discussion on why important genes would be present at sites that are susceptible to inactivation. We offer some answers through a description of known WWOX functions.
Salah
Zaidoun
Z
The Lautenberg Center for Immunology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Pharmacy Building, Jerusalem 91120, Israel. zaidouns@ekmd.huji.ac.il
Aqeilan
Rami
R
Huebner
Kay
K
D043283:Chromosome Fragile Sites; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase
D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human