RIPK1
RIPK1 (Receptor-interacting serine/threonine-protein kinase 1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Chronic lymphocytic leukaemia.
Overview
Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways. Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signalling and cell survival. Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signalling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway.
IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · RIPK1 (Receptor-interacting serine/threonine-protein kinase 1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Chronic lymphocytic leukaemia.
- 1 · What it is
RIPK1 (Receptor-interacting serine/threonine-protein kinase 1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Chronic lymphocytic leukaemia.
- 2 · What goes wrong in cancer
Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways.
- 3 · How drugs use it
No product in this corpus aims at RIPK1 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:10019 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q13546 (protein name, function text, keywords and locations (REST API)); IntOGen RIPK1 (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways. Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signalling and cell survival. Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signalling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway. Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis. RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis. In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyses phosphorylation of MLKL upon induction by ZBP1. Location: Cytoplasm; Cell membrane (UniProt). Locus 6p25.2 (HGNC).
- Chronic lymphocytic leukaemia: IntOGen driver in 1 cohort (CLLSLL)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"RIPK1" OR ABSTRACT:"RIPK1" OR TITLE:"receptor interacting serine/threonine kinase 1" OR ABSTRACT:"receptor interacting serine/threonine kinase 1" OR TITLE:"Receptor-interacting serine/threonine-protein kinase 1" OR ABSTRACT:"Receptor-interacting serine/threonine-protein kinase 1" OR TITLE:"RIP1" OR ABSTRACT:"RIP1" OR TITLE:"RIP-1" OR ABSTRACT:"RIP-1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about RIPK1, not a curated reading list.