The Lautenberg Center for Immunology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Pharmacy Building, Jerusalem 91120, Israel.
Future Oncol. 2010 Feb;6(2):249-59. doi: 10.2217/fon.09.152.
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.
WWOX 基因是一个典型的脆性基因，包含 16q23.2 上的染色体脆性位点，编码大约 46kDa 的 Wwox 蛋白，其 WW 结构域与越来越多有趣的蛋白相互作用。如果一个蛋白的功能由与其相互作用的蛋白决定，那么 Wwox 参与了骨和生殖细胞发育、细胞和动物生长和死亡、转录控制以及抑制癌症发展的众多重要信号通路。由于脆性位点基因的改变对复制应激诱导的 DNA 损伤非常敏感，因此科学界一直在讨论这种基因表达的改变是否为肿瘤细胞克隆扩增提供了选择性优势，以及关于为什么重要基因会存在于易失活的位点的平行讨论。我们通过描述已知的 WWOX 功能提供了一些答案。
