家庭主体相互作用蛋白激酶2通过降低转录核心压缩器CtBP的调节来促进亡
Qinghong Zhang1, Yasuhiro Yoshimatsu, Jeffrey Hildebrand
1Vollum Institute, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA. zhangq@ohsu.edu
Cell
|October 22, 2003
概括
CtBP (C端结合蛋白) 的遗传淘汰会增加亡. 紫外线辐射和HIPK2 (家庭主体相互作用蛋白激酶2) 降低了CtBP水平,促进了p53缺乏细胞的亡.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 转录核抑制剂CtBP (C端结合蛋白) 在调节基因表达方面发挥作用.
- 在小鼠胚胎纤维细胞中CtBP淘汰导致亡的增加.
- 了解CtBP调节对于破译亡途径至关重要.
研究的目的:
- 确定调节细胞CtBP水平的途径及其在亡中的作用.
- 调查CtBP,HIPK2 (家庭基因相互作用蛋白激酶2) 和UV诱导的亡之间的联系.
主要方法:
- 使用E1A-CtBP复合物的小鼠胚胎cDNA库的查.
- 利用基因淘汰,siRNA和基因酶不活性突变体来研究蛋白质功能.
- 评估p53缺乏细胞中的亡诱导.
主要成果:
- 鉴定出HIPK2是一种与CtBP相互作用的蛋白质.
- 通过蛋白质酶介导的降解,HIPK2表达或紫外线照射降低了CtBP水平.
- 紫外线诱导的CtBP降低取决于HIPK2激酶活性.
- 降低CtBP水平促进了细胞亡,即使在p53缺乏的细胞中.
结论:
- 已经阐明了一种UV诱导的亡的新途径,涉及HIPK2-介导的CtBP降解.
- 这种途径在缺乏p53的细胞中是功能性的,为替代的亡机制提供了洞察力.
- 研究结果强调CtBP调节是细胞亡的关键因素.
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