CHD5 is a tumor suppressor at human 1p36
CHD5 is a tumor suppressor at human 1p36
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DOI：
10.1016/j.cell.2006.11.052
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发表时间：
2007-02-09
期刊：
影响因子：
64.5
通讯作者：
Mills, Alea A.
中科院分区：
文献类型：
--
作者：
Bagchi, Anindya;Papazoglu, Cristian;Mills, Alea A.
癌症基因的发现广泛依赖于分析肿瘤的得失，以分别揭示癌基因和抑癌基因的位置。1p36缺失是人类癌症中非常常见的遗传损伤，发生在上皮性、神经性和造血源性的恶性肿瘤中。尽管这表明1p36含有一种在失活时驱动肿瘤发生的基因，但这种肿瘤抑制因子的身份仍然难以捉摸。在这里，我们使用染色体工程来生成小鼠模型，该模型具有与人类1p36相对应的区域的获得和丢失。这种方法从功能上确定了嗜铬区域解旋酶DNA结合域5(ChD5)是一种肿瘤抑制因子，通过p19(Arf)/P53途径控制细胞的增殖、凋亡和衰老。我们证明了CHD5在体内具有肿瘤抑制作用，并与人类癌症中CHD5的缺失有关。这种肿瘤抑制因子的发现为探索癌症的创新临床干预措施提供了新的途径。
Cancer gene discovery has relied extensively on analyzing tumors for gains and losses to reveal the location of oncogenes and tumor suppressor genes, respectively. Deletions of 1p36 are extremely common genetic lesions in human cancer, occurring in malignancies of epithelial, neural, and hematopoietic origin. Although this suggests that 1p36 harbors a gene that drives tumorigenesis when inactivated, the identity of this tumor suppressor has remained elusive. Here we use chromosome engineering to generate mouse models with gain and loss of a region corresponding to human 1p36. This approach functionally identifies chromodomain helicase DNA binding domain 5 (Chd5) as a tumor suppressor that controls proliferation, apoptosis, and senescence via the p19(Arf)/p53 pathway. We demonstrate that Chd5 functions as a tumor suppressor in vivo and implicate deletion of CHD5 in human cancer. Identification of this tumor suppressor provides new avenues for exploring innovative clinical interventions for cancer.