The primary antibodies used to detect p-MLKL (ab196436) and RIPK3
(ab56164) were purchased from Abcam (UK).
When FADD or caspase-8 is inactivated or absent, RIPK1 and TRIF include a RIP homotypic interaction motif (RHIM) domain that permits RIPK3
activation via RHIM-mediated interactions.
Schneider et al., "The necroptosis-inducing kinase RIPK3
dampens adipose tissue inflammation and glucose intolerance," Nature Communications, vol.
Receptor-interacting protein kinase 3 (RIPK3
) is a key component of the necrosome [16, 17] and was reported to be activated in the livers of mouse models after chronic ethanol feeding as well as in the livers of ALD patients .
Mildenhall et al., "RIPK3
promotes cell death and NLRP3 inflammasome activation in the absence of MLKL," Nature Communications, vol.
Maltzman et al., "RIPK3
deficiency or catalytically inactive RIPK1 provides greater benefit than MLKL deficiency in mouse models of inflammation and tissue injury," Cell Death and Differentiation, vol.
Necroptosis is initiated through tumour necrosis factor receptor activation and depends on the serinethreonine kinase receptor-interacting proteins 1 (RIPK1) and 3 (RIPK3
) and other proteins.
Okamoto et al., "TNF can activate RIPK3
and cause programmed necrosis in the absence of RIPK1," Cell Death & Disease, vol.
In a corroborative study, TLR3 agonism induced apoptosis in pSS SGECs through upregulation of RIPK3
, p-FADD, and cleaved caspase-8 .
Indeed, a most recent study revealed that phosphorylation and oxidation of CaMKII mediate regulated necrosis downstream of RIPK3
Recent studies have indicated a previously unknown form of programmed necrosis called necroptosis, which is regulated by the RIPK1 and RIPK3
. In particular, a kinase complex consisted of the RIPK1 and RIPK3
is a central step in the programmed necrotic cell death .