RIP3

RIP3, also known as Receptor-interacting protein kinase 3, is a serine/threonine kinase encoded by the RIPK3 gene in humans. It is a key mediator of programmed necrosis, a form of regulated cell death that differs from apoptosis. RIP3 plays a critical role in initiating necroptosis, a process that involves the activation of the mixed lineage kinase domain-like protein (MLKL). Upon activation, MLKL oligomerizes and translocates to the plasma membrane, leading to membrane permeabilization and cell lysis.

The activation of RIP3 can be triggered by various stimuli, including tumor necrosis factor-alpha (TNF-α) and other death receptor ligands. In response to these signals, RIP3 forms a necrosome complex with other proteins, such as RIPK1 and MLKL. This complex then phosphorylates and activates MLKL, driving the downstream events of necroptosis. Dysregulation of RIP3 signaling has been implicated in a range of diseases, including inflammatory disorders, neurodegenerative conditions, and cancer.

Research into RIP3 has revealed its complex role in cellular processes beyond programmed necrosis. It has been shown to influence immune responses, cell proliferation, and differentiation. The precise mechanisms by which RIP3 exerts these diverse functions are still under investigation. Therapeutic strategies targeting RIP3 are being explored for their potential to modulate cell death pathways in various pathological contexts.