摘要
自噬是哺乳动物细胞内控制错误折叠蛋白和受损细胞器降解的重要机制,营养、氨基酸以及细胞因子的缺乏均能诱导自噬.在自噬的信号通路中,一些自噬蛋白已被证明受到乙酰化修饰的调控,进而影响其催化活性的发挥.但是没有研究证明微管结合蛋白1轻链3(LC3)是否受到乙酰化调控.该研究证明了在血清饥饿诱导的自噬过程中,LC3B-Ⅱ的乙酰化程度大幅降低.HDAC6特异性抑制剂tubacin处理细胞后,LC3B-Ⅱ的乙酰化修饰程度随之升高.同时,血清饥饿条件下,抑制HDAC6的催化活性降低了自噬通路的降解能力.该研究结果表明在血清饥饿诱导的自噬过程中,LC3B-Ⅱ发生去乙酰化,其去乙酰化调控蛋白可能是HDAC6,抑制HDAC6的催化活性会减少自噬途径蛋白的降解.HDAC6介导的LC3乙酰化修饰为自噬降解和自噬蛋白调控的研究提供了新思路.
Autophagy is a critical mechanism controlling the degradation of misfolded proteins and damaged organelles in eukaryotes and can be induced by nutrient withdrawal such as serum starvation. Although differential acetylation of autophagy-related proteins has been reported to be involved in autoph- agic flux, the regulation of acetylated microtubule-associated protein 1 light chain 3 （ LC3 ） is incomplete- ly studied. In the present study, we found that the acetylation levels of phosphotidylethanolamine （PE） - conjugated LC3B （LC3B-II） were profoundly decreased in HeLa cells upon autophagy induction by ser- um starvation. Treatment of the cells with tubacin, a specific inhibitor of histone deacetylase 6 （HDAC6）, inhibited the acetylation of LC3B-II. Meanwhile, suppression of HDAC6 reduced autophagic degradation. Collectively, this study demonstrate that HDAC6 is involved in the regulation of the deacety- lation of LC3B-II during autophagy, and the impairment of such process may block the autophagic flux.Therefore, HDAC6-mediated LC3 acetylation provides a new way for investigating the autophagic degra- dation and autophagic protein regulation.
出处
《暨南大学学报（自然科学与医学版）》
CAS
CSCD
北大核心
2013年第5期517-521,共5页
Journal of Jinan University(Natural Science & Medicine Edition)
基金
国家“十二五”“重大新药创制”科技重大专项(2011ZX09307-303-03)
