RIPK1
RIPK1 (receptor-interacting serine/threonine-protein kinase 1, also known as RIP, RIP1 and RIP-1) is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory signalling. It acts both as a kinase and as a scaffold protein, depending on cellular context. Browse Assay Genie's current range of RIPK1 research reagents below, or read on for the biology behind the target.
RIPK1 has two distinct modes of action. Its kinase-independent scaffold function promotes cell survival and inflammatory signalling: when TNF binds TNFR1, RIPK1 is recruited to the TNF-R1 signalling complex (complex I), where it helps activate the canonical NF-kappa-B pathway. Its kinase activity, by contrast, is essential for regulating the two parallel forms of cell death. Once activated, it directs assembly of complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, or complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis.
Under normal conditions RIPK1 restrains cell death. It is required to limit CASP8-dependent, TNFR1-induced apoptosis, and it inhibits RIPK3-dependent necroptosis through FADD-mediated recruitment of CASP8, which cleaves RIPK1. During embryonic development it prevents TRADD from interacting with FADD, limiting aberrant CASP8 activation. RIPK1 also promotes transcription of pro-inflammatory cytokines such as interleukin-6, and is required for ZBP1-induced NF-kappa-B activation in response to DNA damage. It phosphorylates RIPK3, with the two kinases undergoing reciprocal auto- and trans-phosphorylation, and phosphorylates DAB2IP in a TNF-dependent manner, activating the MAP3K5-JNK apoptotic cascade.
The RIPK1 gene encodes a member of the receptor-interacting protein family of serine/threonine kinases, which belongs to the TKL Ser/Thr protein kinase family within the protein kinase superfamily. HGNC places it in the ripoptosome gene group, and its previous name was receptor (TNFRSF)-interacting serine-threonine kinase 1. The protein is found in the cytoplasm and at the cell membrane. Genetic disruption of the mouse ortholog, Ripk1, causes death shortly after birth, underlining its role in developmental regulation, tissue damage responses and pathogen recognition.
RIPK1 and RIPK3 kinase-mediated necrosis is termed necroptosis, and RIPK1 sits at the core of complex IIb assembly with RIPK3 and MLKL.
RIPK1 limits CASP8-dependent TNFR1-induced apoptosis and drives complex IIa formation with FADD and CASP8 when its kinase activity is engaged.
Recruited to TNF-R1 complex I, RIPK1 acts as a scaffold that promotes cell survival in part by activating the canonical NF-kappa-B pathway.
RIPK1 contributes to inflammatory cytokine production and to inhibition of cell death in embryonic development, with loss in mice causing early postnatal death.
RIPK1 is a serine/threonine kinase that regulates TNF-mediated apoptosis, necroptosis and inflammation. As a scaffold it promotes survival through NF-kappa-B activation; as an active kinase it controls assembly of the death-inducing complexes IIa and IIb. It also phosphorylates RIPK3.
RIPK1 is also called RIP, RIP1 and RIP-1, and was previously named receptor (TNFRSF)-interacting serine-threonine kinase 1. The official full name is receptor interacting serine/threonine kinase 1. UniProt lists it as receptor-interacting serine/threonine-protein kinase 1, with the EC number 2.7.11.1.
RIPK1 has a mouse ortholog, Ripk1. Genetic disruption of the gene in mice results in death shortly after birth, and the protein is required to inhibit apoptosis and necroptosis during embryonic development. Check the datasheet of any product for its validated reactivity.
Other receptor-interacting protein kinases involved in necroptosis, inflammation and cell death signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13546; product specifications from Assay Genie datasheets.