首页|XRCC6调节RYBP表达的分子机制与功能

XRCC6调节RYBP表达的分子机制与功能

扫码查看
目的 研究X-射线修复交叉互补蛋白6(X-ray repair cross complementing 6,XRCC6)结合和下调RING1和YY1结合蛋白(ring1 and YY1 binding protein,RYBP)表达的分子机制与功能.方法 采用蛋白质免疫共沉淀和免疫荧光方法分析XRCC6与RYBP之间的相互作用;采用Western blot法检测XRCC6对RYBP表达水平的影响;采用Western blot法和蛋白质免疫共沉淀法检验XRCC6对RYBP蛋白稳定性的调节作用;采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative pol-ymerase chain reaction,RT-qPCR)检测XRCC6是否通过RYBP调节基因表达.结果 内源性RYBP与XRCC6之间存在相互作用;XRCC6负性调节RYBP蛋白水平;过表达XRCC6促进RYBP的多聚泛素化和蛋白酶体降解,显著缩短其半衰期;XRCC6负调节H2AK119Ub1,通过调节RYBP抑制下游基因的表达.结论 XRCC6结合并通过蛋白酶体途径下调RYBP表达,进而调节RYBP下游基因的表达.
Molecular Mechanism and Function of XRCC6 Regulates RYBP Expression
Objective To investigate the molecular mechanism and function of X-ray repair cross complementing 6(XRCC6)reg-ulate Ring1 and YY1 binding protein(RYBP)expression.Methods The interaction between XRCC6 and RYBP was analyzed by protein co-immunoprecipitation and immunofluorescence assays.The effect of XRCC6 on RYBP protein level was determined by Western blot-ting.The influence of XRCC6 on the stability of RYBP was detected by Western blotting and protein co-immunoprecipitation assays.Re-al-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine whether XRCC6 regulates gene expres-sion through RYBP.Results There was an interaction between endogenous RYBP and XRCC6,and XRCC6 negatively regulated the lev-el of RYBP protein.Overexpression of XRCC6 promoted polyubiquitination and proteasome degradation of RYBP,and significantly short-ened its half-life.Furthermore,XRCC6 negatively regulated H2AK119Ub1 level and inhibited downstream gene expressions through modulating RYBP.Conclusion XRCC6 interacts with and down-regulates RYBP expression through proteasome pathway,thereby regu-lating the expression of RYBP downstream genes.

XRCC6RYBPProtein interactionProteasome pathwayGene expression regulation

刘薇佳、李唐嫒、陈修远、夏婉娉

展开 >

100005 中国医学科学院基础医学研究所、北京协和医学院基础学院生物化学与分子生物学系

XRCC6 RYBP 蛋白质相互作用 蛋白酶体途径 基因表达调节

2024

医学研究杂志
中国医学科学院

医学研究杂志

CSTPCD
影响因子:0.702
ISSN:1673-548X
年,卷(期):2024.53(12)