压力诱导的酸化和转录因子CHOP (GADD153) 的激活由p38 MAP 激酶
1Department of Medicine, Skirball Institute of Biomolecular Medicine, New York University Medical Center, 10016, NY, USA.
概括
细胞应激通过CHOP (C/EBP同源蛋白) 影响生长和分化. 通过p38 MAP激酶对CHOP的压力诱导酸化增强了其转录活性和细胞分化中的作用.
科学领域:
- 分子生物学分子生物学
- 细胞应激反应的应激反应
- 信号传输 信号传输
背景情况:
- CCAAT/增强剂结合蛋白同源蛋白 (CHOP) 是一种转录因子,参与细胞应激反应.
- 在压力条件下观察到CHOP积累和酸化.
- 特定激酶在CHOP调节中的作用仍然是一个研究领域.
研究的目的:
- 调查p38基激活蛋白激酶 (MAPK) 在CHOP的压力诱导酸化中的作用.
- 确定CHOP酸化对转录活性和脂肪细胞分化的功能影响.
主要方法:
- 在试验室中使用纯化的蛋白质进行激酶测试.
- 使用特定的p38 MAPK抑制剂 (SB203580) 的体内研究.
- 对CHOP转录活性和脂肪分化标记物的分析.
主要成果:
- p38 MAPK在体内直接在血清残留78和81上对CHOP进行酸化.
- 抑制p38 MAPK在体内消除了压力诱导的CHOP酸化.
- 酸化增强了CHOP的转录激活功能.
- 酸化对于CHOP对脂肪细胞分化的抑制作用至关重要.
结论:
- 通过p38 MAPK进行的CHOP酸化是将细胞压力与改变基因表达联系起来的关键机制.
- 这种酸化事件调节了CHOP在转录激活和抑制分化中的功能.
- 在压力下,CHOP在p38信号传递和细胞命运决策之间起到关键的调解作用.
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