hSIR2 ((SIRT1) 作为一个依赖NAD的p53脱乙酶起作用
H Vaziri1, S K Dessain, E Ng Eaton
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Cell
|October 24, 2001
概括
人类的hSIR2 (SIRT1) 基因去乙化蛋白,并抑制瘤抑制剂p53. 这种脱乙基化调节了p53的调节.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- DNA损伤触发了p53乙化,导致细胞生长停止或细胞亡.
- 酵母Sir2的人类同类hSIR2 (SIRT1) 蛋白质与衰老和DNA损伤反应有关.
研究的目的:
- 研究hSIR2 (SIRT1) 在调节p53蛋白活性中的作用.
- 要确定hSIR2 (SIRT1) 是否与p53.3直接相互作用并对其进行修改.
主要方法:
- 研究了人类细胞中hSIR2 (SIRT1) 和p53之间的相互作用.
- 评估了野生类型和催化无活性hSIR2 (SIRT1) 对p53转录活性的影响.
- 测量了p53依赖的亡和放射敏感性.
主要成果:
- hSIR2 (SIRT1) 与p53结合并脱,特别是在C端的Lys382残留物.
- 野生型hSIR2 (SIRT1) 的表达减少了p53的转录活性.
- 不活跃的hSIR2 (SIRT1) 增强了p53依赖的亡和辐射敏感性.
结论:
- hSIR2 (SIRT1) 通过脱乙基化来负面调节p53的功能.
- 通过调节p53活性,SIRT1在DNA损伤反应途径中发挥着关键作用.
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