Regulation of necroptotic cell death

Petrie EJ, Sandow JJ, Jacobsen AV, Smith BJ, Griffin MDW, Lucet IS, Dai W, Young SN, Tanzer MC, Wardak A, Liang L, Cowan AD, Hildebrand JM, Kersten WJA, Lessene G, Silke J, Czabotar PE, Webb AI, Murphy JM. Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis. Nature Communications. 2018 Jun 21;9(1):2422. doi: 10.1038/s41467-018-04714-7.; Feoktistova M, Geserick P, Kellert B, Dimitrova D, Langlais C, Hupe M, Cain K, MacFarlane M, Häcker G, Leverkus M. cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms. Molecular Cell. 2011 Aug;43(3):449–63. doi: 10.1016/j.molcel.2011.06.011.; Vittori D, Vota D, Callero M, Chamorro ME, Nesse A. c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-alpha-induced apoptosis. Cell Biol Int. 2010 May 04;34(6):621–30. doi: 10.1042/cbi20090085. PMID: 20218968.; Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, Deshayes K, Fairbrother WJ, Vucic D. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J Biol Chem. 2008 Sep 05;283(36):24295–9. PMID: 18621737; PMCID: PMC3259840.; Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ, Barker PA. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008 Jun 20;30(6):689–700. doi: 10.1016/j.molcel.2008.05.014. PMID: 18570872.; Golks A, Brenner D, Fritsch C, Krammer PH, Lavrik IN. c-FLIPR, a New Regulator of Death Receptor-induced Apoptosis. Journal of Biological Chemistry. 2005 Apr;280(15):14507–13. doi: 10.1074/jbc.m414425200.; Chang DW, Xing Z, Pan Y, Algeciras-Schimnich A, Barnhart BC, Yaish-Ohad S, Peter ME, Yang X. c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J. 2002 Jul 15;21(14):3704–14. PMID: 12110583; PMCID: PMC125398.

Metabolites



Enzyme

EC Number name full name note
2.3.2.23 E2 ubiquitin-conjugating enzyme S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine:[E2 ubiquitin-conjugating enzyme] ubiquitinyl transferase
2.3.2.26 HECT-type E3 ubiquitin transferase [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming)
2.3.2.27 RING-type E3 ubiquitin transferase [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming; RING-type)
2.3.2.31 RBR-type E3 ubiquitin transferase [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming; RBR-type)
2.4.1.255 protein O-GlcNAc transferase UDP-N-acetyl-D-glucosamine:protein-O-beta-N-acetyl-D-glucosaminyl transferase
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
3.4.22.61 caspase-8
3.6.4.10 non-chaperonin molecular chaperone ATPase ATP phosphohydrolase (polypeptide-polymerizing)


Proteins

Protein ID name full name