南京大学学报（自然科学版）2017，Vol.53Issue(6)：1203-1211,9.DOI:10.13232/j.cnki.jnju.2017.06.023
β-arrestin1/2抑制SphK1蛋白质表达研究
Inhibition of SphK1 expression by β-arrestin1/2
摘要
Abstract
Sphingosine kinase type 1(SphK1)is a critical regulator of sphingolipid metabolites.Increasing evidence indicates that SphK1 is highly expressed in human liver cancer,and up regulation of SphK1 expression promotes cancer cell growth and metastasis.In contrast,down regulation of SphK1 expression triggers cancer cell apoptosis suggests the SphK1 could be a potential target for liver cancer therapy.However,the underlying mechanism for SphK1 degradation remains unclear.Here,western blotting,quantitative RT-PCR,and small interfering RNA (siRNA)technologies were used to investigate the mechanism of SphK1 degradation.As a result,the expression of both exogenous and endogenous SphK1 were significantly up-regulated when HEK293T cells and HepG2 cells were treated with the proteasome inhibitor MG132.Moreover,the forced over-expression of β-arrestin1/2 dose-dependently suppressed SphK1 protein level,and this effect could be attenuated by MG132.Knockdown of β-arrestin1/2 expressions in HEK293T cells and HepG2 cells led to a significant increase in cellular SphK1 protein level.In conclusion,β-arrestin1/2 could promote SphK1 degradation probably through ubiquitin-mediated pathway, the result of which offers theoretical basis for the development of specific SphK1 inhibitor.关键词
β-arrestin1/2/神经鞘氨醇激酶1(SphK1)/泛素化/蛋白质降解Key words
β-arrestin1/2/SphK1/ubiquitination/protein degradation分类
生物科学引用本文复制引用
刘永健,卞金俊,花金宝,吴跃军,陈妍,殷武..β-arrestin1/2抑制SphK1蛋白质表达研究[J].南京大学学报（自然科学版）,2017,53(6):1203-1211,9.基金项目
国家自然科学基金(81473293,81171843,81673462,81671939,91540119),上海市科委项目(15411963200),中国博士后科学基金(2016M591365),江苏省重点研发项目(BE2017712),江苏省中医管理局(LZ13230) （81473293,81171843,81673462,81671939,91540119）
