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Future Oncol. 2010 Feb;6(2):249-59. doi: 10.2217/fon.09.152.

WWOX gene and gene product: tumor suppression through specific protein interactions.

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The Lautenberg Center for Immunology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Pharmacy Building, Jerusalem 91120, Israel.


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.

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