RIPK3
Template:Short description Template:Cs1 config Lua error in Module:Infobox_gene at line 53: attempt to index field 'wikibase' (a nil value). Receptor-interacting serine/threonine-protein kinase 3 is an enzyme that is encoded by the RIPK3 gene in humans.[1][2][3][4]
The product of this gene is a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. It contains a C-terminal domain unique from other RIP family members. The encoded protein is predominantly localized to the cytoplasm, and can undergo nucleocytoplasmic shuttling dependent on novel nuclear localization and export signals. It is a component of the tumor necrosis factor (TNF) receptor-I signaling complex, and can induce necroptosis by interaction with RIPK1 and MLKL in a protein complex termed the necrosome.[3] Interactions between RIPK1 and RIPK3 also form a necrosome, which triggers apoptosis.[5]
Interactions
RIPK3 has been shown to interact with RIPK1 to form an amyloid spine[1][4] The RIP Homotypic Interaction Motifs (RHIM) of RIPK3 allows it to form a necrosome with RIPK1.[5] This interaction makes heterotypic β sheets, which bind together to form an alternating "ladder" of Serine from RIPK1 and Cysteine from RIPK3.[5]
Clinical significance
RIPK3 is believed to contribute to lung inflammation and injury during severe infections with the influenza A virus. The experimental RIPK3 inhibitor UH15-38 has shown potential in preclinical studies to reduce mortality and lung damage in mice infected with influenza, indicating that RIPK3 may serve as a therapeutic target for managing hyper-inflammatory conditions such as influenza-related acute respiratory distress syndrome (ARDS).[7][8][9]
References
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- ^ a b Page Module:Citation/CS1/styles.css has no content.Yu PW, Huang BC, Shen M, Quast J, Chan E, Xu X, et al. (May 1999). "Identification of RIP3, a RIP-like kinase that activates apoptosis and NFkappaB". Current Biology. 9 (10): 539–542. Bibcode:1999CBio....9..539Y. doi:10.1016/S0960-9822(99)80239-5. PMID 10339433.
- ^ Page Module:Citation/CS1/styles.css has no content.Sun X, Lee J, Navas T, Baldwin DT, Stewart TA, Dixit VM (June 1999). "RIP3, a novel apoptosis-inducing kinase". The Journal of Biological Chemistry. 274 (24): 16871–16875. doi:10.1074/jbc.274.24.16871. PMID 10358032.
- ^ a b Page Module:Citation/CS1/styles.css has no content."Entrez Gene: RIPK3 receptor-interacting serine-threonine kinase 3".
- ^ a b Page Module:Citation/CS1/styles.css has no content.Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, et al. (July 2012). "The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis". Cell. 150 (2): 339–350. doi:10.1016/j.cell.2012.06.019. PMC 3664196. PMID 22817896.
- ^ a b c Page Module:Citation/CS1/styles.css has no content.Mompeán M, Li W, Li J, Laage S, Siemer AB, Bozkurt G, et al. (May 2018). "The Structure of the Necrosome RIPK1-RIPK3 Core, a Human Hetero-Amyloid Signaling Complex". Cell. 173 (5): 1244–1253.e10. doi:10.1016/j.cell.2018.03.032. PMC 6002806. PMID 29681455.
- ^ Page Module:Citation/CS1/styles.css has no content."RIPK3 - Receptor-interacting serine/threonine-protein kinase 3 - Homo sapiens (Human) - RIPK3 gene & protein". www.uniprot.org. Retrieved 2022-05-13.
- ^ Page Module:Citation/CS1/styles.css has no content.Cao X, Tan J, Zheng R, Wang F, Zhou L, Yi J, et al. (28 August 2024). "Targeting necroptosis: a promising avenue for respiratory disease treatment". Cell Communication and Signaling. 22 (1): 418. doi:10.1186/s12964-024-01804-6. ISSN 1478-811X. PMC 11350980. PMID 39192326.
- ^ Page Module:Citation/CS1/styles.css has no content.Gautam A, Boyd DF, Nikhar S, Zhang T, Siokas I, Van de Velde LA, et al. (April 2024). "Necroptosis blockade prevents lung injury in severe influenza". Nature. 628 (8009): 835–843. Bibcode:2024Natur.628..835G. doi:10.1038/s41586-024-07265-8. PMC 11151938. PMID 38600381.
- ^ Page Module:Citation/CS1/styles.css has no content.Halford B (10 April 2024). "Compound prevents flu-related lung damage in mice". Chemical & Engineering News. Retrieved 5 November 2024.
Further reading
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- Page Module:Citation/CS1/styles.css has no content.Kasof GM, Prosser JC, Liu D, Lorenzi MV, Gomes BC (May 2000). "The RIP-like kinase, RIP3, induces apoptosis and NF-kappaB nuclear translocation and localizes to mitochondria". FEBS Letters. 473 (3): 285–291. Bibcode:2000FEBSL.473..285K. doi:10.1016/S0014-5793(00)01473-3. PMID 10818227.
- Page Module:Citation/CS1/styles.css has no content.Sun X, Yin J, Starovasnik MA, Fairbrother WJ, Dixit VM (March 2002). "Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3". The Journal of Biological Chemistry. 277 (11): 9505–9511. doi:10.1074/jbc.M109488200. PMID 11734559.
- Page Module:Citation/CS1/styles.css has no content.Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Page Module:Citation/CS1/styles.css has no content.Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.
- Page Module:Citation/CS1/styles.css has no content.Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, et al. (May 2004). "RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation" (PDF). Nature Immunology. 5 (5): 503–507. doi:10.1038/ni1061. PMID 15064760. S2CID 12570157.
- Page Module:Citation/CS1/styles.css has no content.Yang Y, Ma J, Chen Y, Wu M (September 2004). "Nucleocytoplasmic shuttling of receptor-interacting protein 3 (RIP3): identification of novel nuclear export and import signals in RIP3". The Journal of Biological Chemistry. 279 (37): 38820–38829. doi:10.1074/jbc.M401663200. PMID 15208320.
- Page Module:Citation/CS1/styles.css has no content.Yang Y, Hu W, Feng S, Ma J, Wu M (June 2005). "RIP3 beta and RIP3 gamma, two novel splice variants of receptor-interacting protein 3 (RIP3), downregulate RIP3-induced apoptosis". Biochemical and Biophysical Research Communications. 332 (1): 181–187. doi:10.1016/j.bbrc.2005.04.114. PMID 15896315.
- Page Module:Citation/CS1/styles.css has no content.Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Page Module:Citation/CS1/styles.css has no content.Zhao L, Wang G, Lu D, Wu J, Song F, Dong J, et al. (June 2006). "Homocysteine, hRIP3 and congenital cardiovascular malformations". Anatomy and Embryology. 211 (3): 203–212. doi:10.1007/s00429-005-0074-9. PMID 16429275. S2CID 7176317.
- Page Module:Citation/CS1/styles.css has no content.Feng S, Ma L, Yang Y, Wu M (September 2006). "Truncated RIP3 (tRIP3) acts upstream of FADD to induce apoptosis in the human hepatocellular carcinoma cell line QGY-7703". Biochemical and Biophysical Research Communications. 347 (3): 558–565. doi:10.1016/j.bbrc.2006.06.118. PMID 16844082.
- Page Module:Citation/CS1/styles.css has no content.Ahn KS, Sethi G, Krishnan K, Aggarwal BB (January 2007). "Gamma-tocotrienol inhibits nuclear factor-kappaB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and potentiation of apoptosis". The Journal of Biological Chemistry. 282 (1): 809–820. doi:10.1074/jbc.M610028200. PMID 17114179.
