生物
DNA损伤
抑制器
细胞凋亡
癌变
癌症研究
抑癌基因
DNA
细胞生物学
P53蛋白
遗传学
癌症
作者
Y Wang,Z Wang,Bharat Joshi,Raj K. Puri,Brian G. Stultz,Qing Yuan,Yujie Bai,Pingkun Zhou,Zengqiang Yuan,Deborah A. Hursh,Xiaolin Bi
出处
期刊:Oncogene
[Springer Nature]
日期:2012-09-10
卷期号:32 (33): 3857-3866
被引量:5
摘要
We previously identified Caliban (Clbn) as the Drosophila homolog of human Serologically defined colon cancer antigen 1 gene and demonstrated that it could function as a tumor suppressor in human non-small-cell lung cancer (NSCLC) cells, although its mode of action was unknown. Herein, we identify roles for Clbn in DNA damage response. We generate clbn knockout flies using homologous recombination and demonstrate that they have a heightened sensitivity to irradiation. We show that normal Clbn function facilitates both p53-dependent and -independent DNA damage-induced apoptosis. Clbn coordinates different apoptosis pathways, showing a two-stage upregulation following DNA damage. Clbn has proapoptotic functions, working with both caspase and the proapoptotic gene Hid. Finally, ecotopic expression of clbn(+) in NSCLC cells suppresses tumor formation in athymic nude mice. We conclude that Caliban is a regulator of DNA damage-induced apoptosis, functioning as a tumor suppressor in both p53-dependent and -independent pathways.
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