RIPK1

RIPK1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRIPK1, RIP, RIP1, RIP-1, receptor interacting serine/threonine kinase 1
External IDsMGI: 108212 HomoloGene: 2820 GeneCards: RIPK1
Gene location (Human)
Chr.Chromosome 6 (human)[1]
BandNo data availableStart3,063,991 bp[1]
End3,115,187 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

8737

19766

Ensembl

ENSG00000137275

ENSMUSG00000021408

UniProt

Q13546

Q60855

RefSeq (mRNA)

NM_003804
NM_001317061

NM_009068

RefSeq (protein)

NP_001303990
NP_003795

NP_033094

Location (UCSC)Chr 6: 3.06 – 3.12 MbChr 6: 34 – 34.04 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Receptor-interacting serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the RIPK1 gene.[5][6][7] RIPK1 is known to have function in a variety of cellular pathways including the NF-κB pathway and programmed necrotic cell death (necroptosis).

Function

Although, RIPK1 has been primarily studied in the context of TNFR signaling, RIPk1 is also activated in response to diverse stimuli.[8]

The kinase domain, while important for necroptotic (programmed necrotic) functions, it appears dispensable for pro-survival roles. Kinase activity of RIPK1 is also required for RIPK1-dependent apoptosis in conditions of IAP1/2 depletion, TAK1inhibition/depletion, RIPK3 depletion or MLKL depletion.[9][10] Also, proteolytic processing of RIPk1, through both caspase-dependent and -independent mechanisms, triggers lethality that is dependent on the generation of one or more specific C-terminal cleavage product(s) of RIPk1 upon stress.

Interactions

RIPK1 has been shown to interact with:

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000137275 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021408 - Ensembl, May 2017
  3. "Human PubMed Reference:".
  4. "Mouse PubMed Reference:".
  5. Stanger BZ, Leder P, Lee TH, Kim E, Seed B (June 1995). "RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death". Cell. 81 (4): 513–23. PMID 7538908. doi:10.1016/0092-8674(95)90072-1.
  6. 1 2 3 4 Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV (June 1996). "TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex". Immunity. 4 (4): 387–96. PMID 8612133. doi:10.1016/S1074-7613(00)80252-6.
  7. "Entrez Gene: RIPK1 receptor (TNFRSF)-interacting serine-threonine kinase 1".
  8. Vanlangenakker N, Vanden Berghe T, Vandenabeele P (January 2012). "Many stimuli pull the necrotic trigger, an overview". Cell Death Differ. 19 (1): 75–86. PMC 3252835Freely accessible. PMID 22075985. doi:10.1038/cdd.2011.164.
  9. Dondelinger, Y; Aguileta, MA; Goossens, V; Dubuisson, C; Grootjans, S; Dejardin, E; Vandenabeele, P; Bertrand, MJ (Oct 2013). "RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition". Cell Death Differ. 20 (10): 1381–92. PMC 3770330Freely accessible. PMID 23892367. doi:10.1038/cdd.2013.94.
  10. Remijsen, Q; Goossens, V; Grootjans, S; Van; den Haute, C; Vanlangenakker, N; Dondelinger, Y; Roelandt, R; Bruggeman, I; Goncalves, A; Bertrand, MJ; Baekelandt, V; Takahashi, N; Berghe, TV; Vandenabeele, P (Jan 2014). "Depletion of RIPK3 or MLKL blocks TNF-driven necroptosis and switches towards a delayed RIPK1 kinase-dependent apoptosis". Cell Death Dis. 5 (1): e1004. doi:10.1038/cddis.2013.531.
  11. 1 2 3 4 Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ, Barker PA (June 2008). "cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination". Mol. Cell. 30 (6): 689–700. PMID 18570872. doi:10.1016/j.molcel.2008.05.014.
  12. 1 2 Liao W, Xiao Q, Tchikov V, Fujita K, Yang W, Wincovitch S, Garfield S, Conze D, El-Deiry WS, Schütze S, Srinivasula SM (May 2008). "CARP-2 is an endosome-associated ubiquitin ligase for RIP and regulates TNF-induced NF-kappaB activation". Curr. Biol. 18 (9): 641–9. PMC 2587165Freely accessible. PMID 18450452. doi:10.1016/j.cub.2008.04.017.
  13. 1 2 Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (September 2000). "Activation of the NF-kappaB pathway by caspase 8 and its homologs". Oncogene. 19 (39): 4451–60. PMID 11002417. doi:10.1038/sj.onc.1203812.
  14. Oshima S, Turer EE, Callahan JA, Chai S, Advincula R, Barrera J, Shifrin N, Lee B, Benedict Yen TS, Yen B, Woo T, Malynn BA, Ma A (February 2009). "ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development". Nature. 457 (7231): 906–9. PMC 2642523Freely accessible. PMID 19060883. doi:10.1038/nature07575.
  15. Kataoka T, Budd RC, Holler N, Thome M, Martinon F, Irmler M, Burns K, Hahne M, Kennedy N, Kovacsovics M, Tschopp J (June 2000). "The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways". Curr. Biol. 10 (11): 640–8. PMID 10837247. doi:10.1016/S0960-9822(00)00512-1.
  16. 1 2 Duan H, Dixit VM (January 1997). "RAIDD is a new 'death' adaptor molecule". Nature. 385 (6611): 86–9. PMID 8985253. doi:10.1038/385086a0.
  17. Ahmad M, Srinivasula SM, Wang L, Talanian RV, Litwack G, Fernandes-Alnemri T, Alnemri ES (February 1997). "CRADD, a novel human apoptotic adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting protein RIP". Cancer Res. 57 (4): 615–9. PMID 9044836.
  18. Yu PW, Huang BC, Shen M, Quast J, Chan E, Xu X, Nolan GP, Payan DG, Luo Y (May 1999). "Identification of RIP3, a RIP-like kinase that activates apoptosis and NFkappaB". Curr. Biol. 9 (10): 539–42. PMID 10339433. doi:10.1016/S0960-9822(99)80239-5.
  19. Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, Damko E, Moquin D, Walz T, McDermott A, Chan FK, Wu H (July 2012). "The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis". Cell. 150 (2): 339–50. PMC 3664196Freely accessible. PMID 22817896. doi:10.1016/j.cell.2012.06.019.
  20. Shembade N, Parvatiyar K, Harhaj NS, Harhaj EW (March 2009). "The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling". EMBO J. 28 (5): 513–22. PMC 2657574Freely accessible. PMID 19131965. doi:10.1038/emboj.2008.285.
  21. Chen D, Li X, Zhai Z, Shu HB (May 2002). "A novel zinc finger protein interacts with receptor-interacting protein (RIP) and inhibits tumor necrosis factor (TNF)- and IL1-induced NF-kappa B activation". J. Biol. Chem. 277 (18): 15985–91. PMID 11854271. doi:10.1074/jbc.M108675200.
  22. Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J (June 1999). "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation". EMBO J. 18 (11): 3044–53. PMC 1171386Freely accessible. PMID 10356400. doi:10.1093/emboj/18.11.3044.
  23. Kim JW, Choi EJ, Joe CO (September 2000). "Activation of death-inducing signaling complex (DISC) by pro-apoptotic C-terminal fragment of RIP". Oncogene. 19 (39): 4491–9. PMID 11002422. doi:10.1038/sj.onc.1203796.
  24. Blankenship JW, Varfolomeev E, Goncharov T, Fedorova AV, Kirkpatrick DS, Izrael-Tomasevic A, Phu L, Arnott D, Aghajan M, Zobel K, Bazan JF, Fairbrother WJ, Deshayes K, Vucic D (January 2009). "Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1)". Biochem. J. 417 (1): 149–60. PMID 18939944. doi:10.1042/BJ20081885.
  25. 1 2 Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J, Dugger D, Gordon N, Sidhu SS, Fellouse FA, Komuves L, French DM, Ferrando RE, Lam C, Compaan D, Yu C, Bosanac I, Hymowitz SG, Kelley RF, Dixit VM (August 2008). "Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies". Cell. 134 (4): 668–78. PMID 18724939. doi:10.1016/j.cell.2008.07.039.
  26. 1 2 Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, Deshayes K, Fairbrother WJ, Vucic D (September 2008). "c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation". J. Biol. Chem. 283 (36): 24295–9. PMC 3259840Freely accessible. PMID 18621737. doi:10.1074/jbc.C800128200.
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Further reading

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