Mechanisms of Cell Death Flashcards
The cell death wheel
Intrinsic and Extrinsic Apoptosis
Necroptosis
Pyroptosis
Ferroptosis
NETosis
Cuproptosis
TNFa-induced TAK1-RIPK1 signaling
TAK1-mediated RIPK1 phosphorylation dictates the activation multiple cell death pathways. Upon TNFα treatment, TAK1 is activated to mediate RIPK1 phosphorylation on the intermediate domain. Under normal conditions, TNFα/CHX induces transient phosphorylation of RIPK1 S321 by TAK1 and leads to RIPK1-independent apoptosis. Dysregulation of RIPK1 phosphorylation by TAK1 promotes its activation. When the phosphorylation of RIPK1 intermediate domain is blocked as in TAK1 KO cells, with inhibitor of TAK1 or IAP antagonist (SM-164), TNFα alone or TNFα/CHX treatment promotes the activation of RIPK1 and its binding with FADD to mediate RDA. On the other hand, hyperphosphorylation of RIPK1 intermediate domain, as in TNFα-stimulated TAB2 KO and A20 KO cells, promotes its interaction with RIPK3 to mediate necroptosis
Rag-Ragulator regulation of RIPK1