SIRT2 与细胞坏死.ppt

Necrosis ;;背景1;肿瘤坏死因子TNF-a通过刺激RIP1和RIP3形成complex，进而磷酸化下游蛋白MLKL。MLKL将“necrosome”与线粒体磷酸酶PGAM5联系起来。PGAM5的激活可以导致成串排列的线粒体发生线性断裂，这一现象在细胞坏死发生的早期起到了非常重要的作用。 ;;RIP3 as a potential Sirt2 interacting protein;Sirt2 interacts with RIP3;Sirt2 regulates RIP1-RIP3 complex formation;;Absence of a detectable interaction between Sirt2 and RIP1 ;Sirt2 knockdown blocks RIP1-RIP3 complex formation ;Inhibition of SIRT2 prevents cellular necrosis;Inhibition of SIRT2 prevents necrosis by blocking RIP1 and RIP3 interaction;a requirement for SIRT2 in the formation of the RIP1–RIP3 complex;Copy from Wikipedia;Copy from Wikipedia;SIRT2 regulates RIP1 acetylation;SIRT2 regulates RIP1 acetylation;Assessment of endogenous RIP1 acetylation and necrosis;Necrosis brings SIRT2-RIP3 complex and RIP1 in close proximity which facilitates RIP1 deacetylation;necrosis brings RIP3-SIRT2 complex and RIP1 in close proximity.;Question Which Lysine residue was acetylated?;The p300 acetyltransferase regulates RIP1 acetylation ;Acetylation status of RIP1 lysine 530 regulates necrosis;Inhibiting SIRT2 reduces ischaemic injury;The molecular mechanism that regulates Necrosis;Sirt1 expression does not alter RIP1 acetylation