RIPK3 Protein, Human (P.pastoris, His)

RIPK3, a serine/threonine-protein kinase, orchestrates both necroptosis and apoptosis, two distinct forms of programmed cell death. Necroptosis, triggered by death-inducing TNF-alpha family members and activated by ZBP1, involves RIPK3-mediated phosphorylation of MLKL, leading to membrane damage and calcium influx. Additionally, in response to orthomyxovirus infection, nuclear RIPK3, prompted by ZBP1 activation, phosphorylates MLKL, causing nuclear envelope disruption and DNA leakage. RIPK3 also regulates apoptosis, dependent on RIPK1, FADD, and CASP8, independently of MLKL and RIPK3 kinase activity. In certain cell types, RIPK3 restricts viral replication through cell death-independent responses. In the context of Zika virus infection in neurons, RIPK3, along with ZBP1, promotes a death-independent transcriptional program, upregulating ACOD1/IRG1 and itaconate production, inhibiting succinate dehydrogenase, and suppressing viral genome replication. RIPK3 enhances the activity of metabolic enzymes (GLUL, GLUD1, PYGL), potentially influencing the tricarboxylic acid cycle and oxidative phosphorylation. During herpes simplex virus 1 infection, RIPK3 forms heteromeric amyloid structures with HHV-1 protein RIR1/ICP6, potentially inhibiting RIPK3-mediated necroptosis, enabling viral evasion of host cell death pathways.