RIP1 Cleavage in the Kinase Domain Regulates TRAIL-Induced NF-κB Activation and Lymphoma Survival

Cationic PEGylated liposomes incorporating an antimicrobial peptide tilapia hepcidin 2–3: an adjuvant of epirubicin to overcome multidrug resistance in cervical cancer cells

“…Accumulating studies have supported RIP1 as a key moderator of cell survival signaling, while other reports have suggested a prodeath role of RIP1. 22,24,55 Wang et al 22 have found that RIP1 played a crucial role in survival through catalase-mediated ROS reduction and maintenance of inhibitor of apoptosis proteins, thus enhancing chemoresistance to cisplatin in human lung cancer A549 cells. The activation of necropotosis was verified by the induction of RIP1 and RIP3, which was abrogated by necropotosis inhibitor necrostatin-1.…”

“…23 RIP1 transfers signals provoked by various stresses or chemotherapeutic agents to go through survival and death pathways. 22,24 RIP1 was shown to induce TNF-α receptor 1 for subsequent NF-κB stimulation to initiate cell survival. 24 These antiapoptotic-, antiautophagy-, and necropotosis-related cell survival mechanisms usually correspond to nonpump MDR.…”

“…22,24 RIP1 was shown to induce TNF-α receptor 1 for subsequent NF-κB stimulation to initiate cell survival. 24 These antiapoptotic-, antiautophagy-, and necropotosis-related cell survival mechanisms usually correspond to nonpump MDR. To circumvent chemoresistance, it is necessary to concurrently activate apoptosis or autophagy-mediated cancer cell death for effective anticancer drug treatment.…”

The Janus Face of Death Receptor Signaling during Tumor Immunoediting

“…When active, caspase-8 cleaves RIPK1 within its kinase domains (KDs) and intermediate domains (IDs), thus blocking its function (55) (Figure 2). …”

“…While fully processed caspase-8 can inhibit all RIPK1 functions, by cleaving it in its KD and ID, the FLIP (p43) :caspase-8 heterodimer only cleaves RIPK1 in the KD domain. This cleavage, while still permitting recruitment of RIPK1 to the DR and downstream NF-κB activation (55), blocks RIPK1-driven necroptosis (127) (Figure 2B).…”