蛋白质泛素化与健康.pptx

泛素-蛋白酶体途径与健康Ubiquitin-Proteasome Pathway;;Part one;The protein synthesis, modification and degradation;Two protein degradation mechanisms ;The Nobel Prize in Chemistry 2004 for the discovery of ubiquitin-mediated proteolysis ;Part two;E1;Ubiquitin;E1可以水解ATP，催化泛素羧基端腺嘌呤化，形成泛素-腺苷酸中间物，同时释放无机焦磷酸（PPi）。中间物与E1半胱氨酸残基形成E1-Ub硫酯键.;E1（泛素激活酶）; ①.RING finger domain（SCF complex，APC complex；Mdm2，c-Cb1）； ②.U-box domain； ③.HECT domain（containing segments homologous to E6-protein)。;;Deubiquitination ;Part three;? ? ? ?;;26S Proteasome: ATP-dependent Protein hydrolysis complex ;Ubiquitin-Proteasome Pathway;Part four;The significance of UPP in human body ; ① SCF and APC in the cell cycle ;②Mdm2/p53 with Tumor;NF-κB;;CYLD promotes the ubiquitination of TRAF, thereby inhibiting the activity of NF-κB ;N ENGL J MED 2004, 350:187-188;Immunoproteasome;MHC class I antigen presentation pathway;Significance of protein degradation ;Reference：;;;THANK YOU