通过Sir2alpha对p53进行负控制,可以促进细胞在压力下存活
1Institute of Cancer Genetics and Department of Pathology, College of Physicians & Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA.
Cell
|October 24, 2001
概括
哺乳动物Sir2alpha与p53相互作用,抑制其功能并抑制亡. 尼古丁胺 (维生素B3) 阻断了这种脱乙基化,影响了细胞应激反应和癌症治疗.
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:
- Sir2蛋白质是依赖NAD的脱乙酶,将新陈代谢与基因沉默和衰老联系起来.
- 哺乳动物的Sir2同类物,包括Sir2alpha,涉及到各种细胞过程.
研究的目的:
- 研究哺乳动物Sir2alpha与瘤抑制剂p53.3之间的相互作用.
- 阐明Sir2alpha在调节p53介导功能的作用,包括细胞亡和细胞应激反应.
主要方法:
- 同免疫沉试验证明了Sir2alpha和p53.3之间的物理相互作用.
- 在体内和体外实验中评估Sir2alpha对p53乙化和脱乙化的影响.
- 细胞检测测量细胞亡和应激反应在Sir2alpha或其突变的存在.
主要成果:
- 哺乳动物Sir2alpha在物理上与p53相互作用.
- Sir2alpha减弱了p53介导的转录活性和DNA结合.
- 尼古丁胺 (维生素B3) 抑制Sir2alpha诱导的p53脱乙化,并在体内增强p53乙化.
- Sir2alpha抑制由DNA损伤和氧化应激引起的p53-依赖性亡.
- 一个Sir2alpha点突变体的表达使细胞对压力诱导的亡敏感.
结论:
- 哺乳动物Sir2alpha在p53调节途径中发挥着关键作用.
- Sir2alpha调节细胞对p53依赖的亡的敏感性.
- 针对Sir2alpha-p53相互作用可能为癌症提供新的治疗策略.
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