Kaspaza-8

Kaspaza-8
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1F9E, 1I4E, 1QDU, 1QTN, 2C2Z, 2FUN, 2K7Z, 2Y1L, 3H11, 3KJN, 3KJQ, 4JJ7, 4PRZ, 4PS1, 4ZBW
Identifikatori
Aliasi	CASP8
Vanjski ID-jevi	OMIM: 601763 MGI: 1261423 HomoloGene: 7657 GeneCards: CASP8
Lokacija gena (čovjek)
Hrom.	Hromosom 2 (čovjek)
Kraj	201,287,711 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	58,886,662 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• death effector domain binding; • cysteine-type peptidase activity; • cysteine-type endopeptidase activity involved in apoptotic signaling pathway; • scaffold protein binding; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje identičnih proteina; • cysteine-type endopeptidase activity involved in apoptotic process; • cysteine-type endopeptidase activity; • hydrolase activity; • ubiquitin protein ligase binding; • GO:0070122 peptidase activity; • cysteine-type endopeptidase activity involved in execution phase of apoptosis; • death receptor binding; • tumor necrosis factor receptor binding; • GO:0032403 protein-containing complex binding;
Ćelijska komponenta	• cell body; • citosol; • CD95 death-inducing signaling complex; • ripoptosome; • nukleoplazma; • mitochondrial outer membrane; • death-inducing signaling complex; • Lipidni splav; • neuron projection; • citoskelet; • citoplazma; • mitohondrija; • jedro; • GO:0009327 makromolekulani kompleks;
Biološki proces	• regulation of apoptotic process; • response to estradiol; • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; • GO:1904576 response to antibiotic; • regulation of tumor necrosis factor-mediated signaling pathway; • positive regulation of macrophage differentiation; • GO:1904579 cellular response to organic cyclic compound; • natural killer cell activation; • negative regulation of I-kappaB kinase/NF-kappaB signaling; • TRAIL-activated apoptotic signaling pathway; • Proteoliza; • macrophage differentiation; • TRIF-dependent toll-like receptor signaling pathway; • response to tumor necrosis factor; • B cell activation; • cell surface receptor signaling pathway; • response to lipopolysaccharide; • cellular response to mechanical stimulus; • activation of cysteine-type endopeptidase activity; • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; • death-inducing signaling complex assembly; • positive regulation of proteolysis; • positive regulation of I-kappaB kinase/NF-kappaB signaling; • apoptotic signaling pathway; • response to cold; • regulation of extrinsic apoptotic signaling pathway via death domain receptors; • GO:0022415 viral process; • response to ethanol; • response to cobalt ion; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • proteolysis involved in cellular protein catabolic process; • syncytiotrophoblast cell differentiation involved in labyrinthine layer development; • nucleotide-binding oligomerization domain containing signaling pathway; • T cell activation; • suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process; • GO:0097285 apoptoza; • extrinsic apoptotic signaling pathway; • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; • regulation of necroptotic process; • execution phase of apoptosis; • toll-like receptor 3 signaling pathway; • positive regulation of neuron death; • extrinsic apoptotic signaling pathway via death domain receptors; • positive regulation of interleukin-1 beta production;
	Izvori:Amigo / QuickGO
Ortolozi
	841
	12370
	ENSG00000064012
	ENSMUSG00000026029
	Q14790
	O89110
NM_001080124; NM_001080125; NM_001228; NM_033355; NM_033356;
	NM_033357; NM_033358; NM_001372051
	NM_001080126; NM_001277926; NM_009812
NP_001073593; NP_001073594; NP_001219; NP_203519; NP_203520;
	NP_203522; NP_001358980
	NP_001073595; NP_001264855; NP_033942
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Kaspaza-8 je kaspazni protein, kodiran CASP8 genom. To jest proteinski enzim koji je kod ljudi kodiran genom sa hromosoma 2. Najvjerovatnije djeluje na kaspazu-3.

CASP8 ortolozi^[5] identificirani su kod brojnih sisara za koje su dostupni potpuni podaci o genomu. Ovi jedinstveni ortolozi su takođe prisutni u pticama.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 479 aminokiselina, a molekulska težina 55.391 Da.ref name="OrthoMaM"/>

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MDFSRNLYDI	GEQLDSEDLA	SLKFLSLDYI	PQRKQEPIKD	ALMLFQRLQE
KRMLEESNLS	FLKELLFRIN	RLDLLITYLN	TRKEEMEREL	QTPGRAQISA
YRVMLYQISE	EVSRSELRSF	KFLLQEEISK	CKLDDDMNLL	DIFIEMEKRV
ILGEGKLDIL	KRVCAQINKS	LLKIINDYEE	FSKERSSSLE	GSPDEFSNGE
ELCGVMTISD	SPREQDSESQ	TLDKVYQMKS	KPRGYCLIIN	NHNFAKAREK
VPKLHSIRDR	NGTHLDAGAL	TTTFEELHFE	IKPHDDCTVE	QIYEILKIYQ
LMDHSNMDCF	ICCILSHGDK	GIIYGTDGQE	APIYELTSQF	TGLKCPSLAG
KPKVFFIQAC	QGDNYQKGIP	VETDSEEQPY	LEMDLSSPQT	RYIPDEADFL
LGMATVNNCV	SYRNPAEGTW	YIQSLCQSLR	ERCPRGDDIL	TILTEVNYEV
SNKDDKKNMG	KQMPQPTFTL	RKKLVFPSD

Funkcija

Gen CASP8 kodira člana porodice proteaza cistein-asparaginska kiselina (kaspaza). Sekvencna aktivacija kaspaza ima centralnu ulogu u fazi izvršenja ćelijskih apoptoza. Kaspaze postoje kao neaktivni proenzimi sastavljeni od prodomena, velike i maled proteazne podjedinice. Aktivacija kaspaza zahtijeva proteolitsku obradu konzerviranih unutrašnjih asparaginskih ostataka da bi se dobio heterodimerni enzim koji se sastoji od velike i male podjedinice. Ovaj protein je uključen u programiranu smrt ćelije izazvanu Fas-om i raznim apoptotskim stimulansima. Domen efektora smrti nalik N-terminalnom FADD ovog proteina sugerira da on može stupiti u interakciju sa proteinom FADD koji djeluje na Fas. Ovaj protein je otkriven u nerastvorljivoj frakciji zahvaćene regije mozga kod pacijenata sa Huntingtonovom bolešću, ali ne i kod onih iz normalne kontrole, što implicira ulogu u neurodegenerativnim bolestima. Opisane su mnoge alternativno sprerađene varijante transkripta koje kodiraju različite izoforme, iako za sve varijante nisu određene sekvence pune dužine..^[6]

Klinički značaj

Vrlo rijedak genetički poremećaj imunskog sistema također može biti uzrokovan mutacijama ovog gena. Ova bolest, nazvana CEDS, znači "stanje nedostatka kaspaze osam". CEDS ima karakteristike slične ALPS, još jednu genetičku bolest apoptoze, uz dodatak imunodeficijentnog fenotipa. Dakle, kliničke manifestacije uključuju splenomegaliju i limfadenopatiju, pored rekurentnih sinopulmonalnih infekcija, rekurentne mukokutane herpesvirusne, uporne bradavice i infekcije molluscum contagiosum i hipogamaglobulinemija. Ponekad postoji limfocitna infiltrativna bolest u parenhimskim organima, ali autoimunost je minimalna i limfom nije uočen kod pacijenata sa CEDS-om. CEDS se nasljeđuje na autosomno recesivan način.^[7] Klinički fenotip pacijenata sa CEDS-om predstavlja paradoks jer se kaspaza-8 smatrala uglavnom proapoptotskom proteazom, koja je uglavnom bila uključena u transdukciju signala iz receptora faktora nekroze tumora porodične receptore smrti kao što je Fas. Defekt u aktivaciji limfocita i zaštitnoi imunosti sugerira da kaspaza-8 ima dodatnu signalnu ulogu u limfocitima. Dalji rad je otkrio da je kaspaza-8 neophodna za indukciju faktora transkripcije „jedarni faktor κB” (NF-κB), nakon stimulacije preko antigenog receptora, Fc receptora ili Toll-likog receptora 4 u T, B i prirodne ćelije ubice.^[7]

Biohemijski je utvrđeno da kaspaza-8 ulazi u kompleks inhibitora NF-κB kinaza (IKK) sa uzvodnim adapterskim kompleksom Bcl10-MALT1 (mukoza-povezano limfno tkivo) koji su bili ključni za indukcija jedarne translokacije NF-κB. Štaviše, biohemijski oblik kaspaze-8 razlikovao se u dva puta. Za put smrti, zimogen kaspaze-8 cijepa se na podjedinice koje se sastavljaju kako bi formirale zreli, visoko aktivni kaspazni heterotetramer, dok se za put aktivacije čini da zimogen ostaje netaknut možda da bi ograničio njegovu proteolitsku funkciju, ali poboljšao njegovu sposobnost kao adapter proteina.^[7]

Interakcije

Pokazalo se da kaspaza-8 reaguje sa:

BCAP31,^[8]
BID,^[9]^[10]
Bcl-2,^[10]^[11]
CFLAR,^[12]^[13]^[14]^[15]^[16]^[17]^[18]
Kaspaza-10,^[9]^[10]^[12]^[19]
Kaspaza-2,^[10]^[19]
Kaspaza -3,^[10]^[19]
Kaspaza-6,^[10]^[19]^[20]
Kaspaza -7,^[10]^[19]
Kaspaza -9,^[10]^[19]
DEDD,^[21]^[22]^[23]
FADD,^[9]^[12]^[15]^[24]^[25]^[26]^[27]
FasL,^[9]^[12]
FasR,^[9]^[13]^[28]
IFT57,^[29]
NOL3,^[30]
PEA15,^[31]^[32]
RIPK1,^[24]^[33]^[34]
TNFRSF10B,^[9]^[28] i
TRAF1.^[12]^[35]

Dopunske slike

Signalni put TNF-R1. Isprekidane sive linije predstavljaju više koraka

Pregled puteva transdukcija signala uključenih u apoptozu.

Također pogledajte

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000064012 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026029 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "OrthoMaM phylogenetic marker: CASP8 coding sequence".^{[trajno mrtav link]}
^ "Entrez Gene: CASP8 caspase 8, apoptosis-related cysteine peptidase".
^ ^a ^b ^c Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, Lenardo MJ (2002). "Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency". Nature. 419 (6905): 395–9. Bibcode:2002Natur.419..395C. doi:10.1038/nature01063. PMID 12353035. S2CID 4359174.
^ Ng FW, Nguyen M, Kwan T, Branton PE, Nicholson DW, Cromlish JA, Shore GC (oktobar 1997). "p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum". J. Cell Biol. 139 (2): 327–38. doi:10.1083/jcb.139.2.327. PMC 2139787. PMID 9334338.
^ ^a ^b ^c ^d ^e ^f Gajate C, Mollinedo F (mart 2005). "Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy". J. Biol. Chem. 280 (12): 11641–7. doi:10.1074/jbc.M411781200. PMID 15659383.
^ ^a ^b ^c ^d ^e ^f ^g ^h Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (april 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.
^ Poulaki V, Mitsiades N, Romero ME, Tsokos M (juni 2001). "Fas-mediated apoptosis in neuroblastoma requires mitochondrial activation and is inhibited by FLICE inhibitor protein and Bcl-2". Cancer Res. 61 (12): 4864–72. PMID 11406564.
^ ^a ^b ^c ^d ^e Micheau O, Tschopp J (juli 2003). "Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes" (PDF). Cell. 114 (2): 181–90. doi:10.1016/s0092-8674(03)00521-x. PMID 12887920. S2CID 17145731.
^ ^a ^b Shu HB, Halpin DR, Goeddel DV (juni 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751–63. doi:10.1016/s1074-7613(00)80450-1. PMID 9208847.
^ Goltsev YV, Kovalenko AV, Arnold E, Varfolomeev EE, Brodianskii VM, Wallach D (august 1997). "CASH, a novel caspase homologue with death effector domains". J. Biol. Chem. 272 (32): 19641–4. doi:10.1074/jbc.272.32.19641. PMID 9289491.
^ ^a ^b Srinivasula SM, Ahmad M, Ottilie S, Bullrich F, Banks S, Wang Y, Fernandes-Alnemri T, Croce CM, Litwack G, Tomaselli KJ, Armstrong RC, Alnemri ES (juli 1997). "FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis". J. Biol. Chem. 272 (30): 18542–5. doi:10.1074/jbc.272.30.18542. PMID 9228018.
^ Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson DW, Briand C, Grütter MG (novembar 2002). "The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex". J. Biol. Chem. 277 (47): 45162–71. doi:10.1074/jbc.M206882200. PMID 12215447.
^ Han DK, Chaudhary PM, Wright ME, Friedman C, Trask BJ, Riedel RT, Baskin DG, Schwartz SM, Hood L (oktobar 1997). "MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death". Proc. Natl. Acad. Sci. U.S.A. 94 (21): 11333–8. Bibcode:1997PNAS...9411333H. doi:10.1073/pnas.94.21.11333. PMC 23459. PMID 9326610.
^ Roth W, Stenner-Liewen F, Pawlowski K, Godzik A, Reed JC (mart 2002). "Identification and characterization of DEDD2, a death effector domain-containing protein". J. Biol. Chem. 277 (9): 7501–8. doi:10.1074/jbc.M110749200. PMID 11741985.
^ ^a ^b ^c ^d ^e ^f Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (decembar 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.
^ Cowling V, Downward J (oktobar 2002). "Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain". Cell Death Differ. 9 (10): 1046–56. doi:10.1038/sj.cdd.4401065. PMID 12232792.
^ Zhan Y, Hegde R, Srinivasula SM, Fernandes-Alnemri T, Alnemri ES (april 2002). "Death effector domain-containing proteins DEDD and FLAME-3 form nuclear complexes with the TFIIIC102 subunit of human transcription factor IIIC". Cell Death Differ. 9 (4): 439–47. doi:10.1038/sj.cdd.4401038. PMID 11965497.
^ Alcivar A, Hu S, Tang J, Yang X (januar 2003). "DEDD and DEDD2 associate with caspase-8/10 and signal cell death". Oncogene. 22 (2): 291–7. doi:10.1038/sj.onc.1206099. PMID 12527898.
^ Stegh AH, Schickling O, Ehret A, Scaffidi C, Peterhänsel C, Hofmann TG, Grummt I, Krammer PH, Peter ME (oktobar 1998). "DEDD, a novel death effector domain-containing protein, targeted to the nucleolus". EMBO J. 17 (20): 5974–86. doi:10.1093/emboj/17.20.5974. PMC 1170924. PMID 9774341.
^ ^a ^b 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 (februar 2009). "ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development". Nature. 457 (7231): 906–9. Bibcode:2009Natur.457..906O. doi:10.1038/nature07575. PMC 2642523. PMID 19060883.
^ Henshall DC, Araki T, Schindler CK, Shinoda S, Lan JQ, Simon RP (septembar 2003). "Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures". J. Neurochem. 86 (5): 1260–70. doi:10.1046/j.1471-4159.2003.01934.x. PMID 12911633. S2CID 21971958.
^ Boldin MP, Goncharov TM, Goltsev YV, Wallach D (juni 1996). "Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death". Cell. 85 (6): 803–15. doi:10.1016/s0092-8674(00)81265-9. PMID 8681376. S2CID 7415784.
^ Thomas LR, Stillman DJ, Thorburn A (septembar 2002). "Regulation of Fas-associated death domain interactions by the death effector domain identified by a modified reverse two-hybrid screen". J. Biol. Chem. 277 (37): 34343–8. doi:10.1074/jbc.M204169200. PMID 12107169.
^ ^a ^b MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES (oktobar 1997). "Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL". J. Biol. Chem. 272 (41): 25417–20. doi:10.1074/jbc.272.41.25417. PMID 9325248.
^ Gervais FG, Singaraja R, Xanthoudakis S, Gutekunst CA, Leavitt BR, Metzler M, Hackam AS, Tam J, Vaillancourt JP, Houtzager V, Rasper DM, Roy S, Hayden MR, Nicholson DW (februar 2002). "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nat. Cell Biol. 4 (2): 95–105. doi:10.1038/ncb735. PMID 11788820. S2CID 10439592.
^ Koseki T, Inohara N, Chen S, Núñez G (april 1998). "ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases". Proc. Natl. Acad. Sci. U.S.A. 95 (9): 5156–60. Bibcode:1998PNAS...95.5156K. doi:10.1073/pnas.95.9.5156. PMC 20230. PMID 9560245.
^ Kitsberg D, Formstecher E, Fauquet M, Kubes M, Cordier J, Canton B, Pan G, Rolli M, Glowinski J, Chneiweiss H (oktobar 1999). "Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis". J. Neurosci. 19 (19): 8244–51. doi:10.1523/JNEUROSCI.19-19-08244.1999. PMC 6783010. PMID 10493725.
^ Condorelli G, Vigliotta G, Cafieri A, Trencia A, Andalò P, Oriente F, Miele C, Caruso M, Formisano P, Beguinot F (august 1999). "PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis". Oncogene. 18 (31): 4409–15. doi:10.1038/sj.onc.1202831. PMID 10442631. S2CID 20510429.
^ Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (septembar 2000). "Activation of the NF-kappaB pathway by caspase 8 and its homologs". Oncogene. 19 (39): 4451–60. doi:10.1038/sj.onc.1203812. PMID 11002417.
^ Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ, Barker PA (juni 2008). "cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination". Mol. Cell. 30 (6): 689–700. doi:10.1016/j.molcel.2008.05.014. PMID 18570872.
^ Leo E, Deveraux QL, Buchholtz C, Welsh K, Matsuzawa S, Stennicke HR, Salvesen GS, Reed JC (mart 2001). "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". J. Biol. Chem. 276 (11): 8087–93. doi:10.1074/jbc.M009450200. PMID 11098060.

Dopunska literatura

Jia SH, Parodo J, Kapus A, Rotstein OD, Marshall JC (2008). "Dynamic Regulation of Neutrophil Survival through Tyrosine Phosphorylation or Dephosphorylation of Caspase-8". Journal of Biological Chemistry. 283 (9): 5402–5413. doi:10.1074/jbc.M706462200. PMID 18086677.
Cohen GM (1997). "Caspases: the executioners of apoptosis". Biochem. J. 326 (Pt 1): 1–16. doi:10.1042/bj3260001. PMC 1218630. PMID 9337844.
Siegel RM, Chan FK, Chun HJ, Lenardo MJ (2001). "The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity". Nat. Immunol. 1 (6): 469–74. doi:10.1038/82712. PMID 11101867. S2CID 345769.
Ye S, Goldsmith EJ (2002). "Serpins and other covalent protease inhibitors". Curr. Opin. Struct. Biol. 11 (6): 740–5. doi:10.1016/S0959-440X(01)00275-5. PMID 11751056.
Gupta S (2002). "Tumor necrosis factor-alpha-induced apoptosis in T cells from aged humans: a role of TNFR-I and downstream signaling molecules". Exp. Gerontol. 37 (2–3): 293–9. doi:10.1016/S0531-5565(01)00195-4. PMID 11772515. S2CID 30243363.
Pomerantz RJ (2004). "Effects of HIV-1 Vpr on neuroinvasion and neuropathogenesis". DNA Cell Biol. 23 (4): 227–38. doi:10.1089/104454904773819815. PMID 15142380.
Zhao LJ, Zhu H (2005). "Structure and function of HIV-1 auxiliary regulatory protein Vpr: novel clues to drug design". Curr. Drug Targets Immune Endocr. Metabol. Disord. 4 (4): 265–75. doi:10.2174/1568008043339668. PMID 15578977.

Vanjsk linkovi

The MEROPS online database for peptidases and their inhibitors: C14.009^{[mrtav link]}
Apoptosis & Caspase 8—The Proteolysis Map (animation)
Caspase 8 na US National Library of Medicine Medical Subject Headings (MeSH)
caspase-8
Q14790

Portal Biologija

Šablon:Fas apoptozni signalni put

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000064012 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026029 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[OrthoMaM-5] "OrthoMaM phylogenetic marker: CASP8 coding sequence".^{[trajno mrtav link]}

[6] "Entrez Gene: CASP8 caspase 8, apoptosis-related cysteine peptidase".

[Chun_2002-7] Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, Lenardo MJ (2002). "Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency". Nature. 419 (6905): 395–9. Bibcode:2002Natur.419..395C. doi:10.1038/nature01063. PMID 12353035. S2CID 4359174.

[pmid9334338-8] Ng FW, Nguyen M, Kwan T, Branton PE, Nicholson DW, Cromlish JA, Shore GC (oktobar 1997). "p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum". J. Cell Biol. 139 (2): 327–38. doi:10.1083/jcb.139.2.327. PMC 2139787. PMID 9334338.

[pmid15659383-9] ^ ^a ^b ^c ^d ^e ^f Gajate C, Mollinedo F (mart 2005). "Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy". J. Biol. Chem. 280 (12): 11641–7. doi:10.1074/jbc.M411781200. PMID 15659383.

[pmid11832478-10] ^ ^a ^b ^c ^d ^e ^f ^g ^h Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (april 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.

[pmid11406564-11] Poulaki V, Mitsiades N, Romero ME, Tsokos M (juni 2001). "Fas-mediated apoptosis in neuroblastoma requires mitochondrial activation and is inhibited by FLICE inhibitor protein and Bcl-2". Cancer Res. 61 (12): 4864–72. PMID 11406564.

[pmid12887920-12] Micheau O, Tschopp J (juli 2003). "Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes" (PDF). Cell. 114 (2): 181–90. doi:10.1016/s0092-8674(03)00521-x. PMID 12887920. S2CID 17145731.

[pmid9208847-13] Shu HB, Halpin DR, Goeddel DV (juni 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751–63. doi:10.1016/s1074-7613(00)80450-1. PMID 9208847.

[pmid9289491-14] Goltsev YV, Kovalenko AV, Arnold E, Varfolomeev EE, Brodianskii VM, Wallach D (august 1997). "CASH, a novel caspase homologue with death effector domains". J. Biol. Chem. 272 (32): 19641–4. doi:10.1074/jbc.272.32.19641. PMID 9289491.

[pmid9228018-15] Srinivasula SM, Ahmad M, Ottilie S, Bullrich F, Banks S, Wang Y, Fernandes-Alnemri T, Croce CM, Litwack G, Tomaselli KJ, Armstrong RC, Alnemri ES (juli 1997). "FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis". J. Biol. Chem. 272 (30): 18542–5. doi:10.1074/jbc.272.30.18542. PMID 9228018.

[pmid12215447-16] Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson DW, Briand C, Grütter MG (novembar 2002). "The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex". J. Biol. Chem. 277 (47): 45162–71. doi:10.1074/jbc.M206882200. PMID 12215447.

[pmid9326610-17] Han DK, Chaudhary PM, Wright ME, Friedman C, Trask BJ, Riedel RT, Baskin DG, Schwartz SM, Hood L (oktobar 1997). "MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death". Proc. Natl. Acad. Sci. U.S.A. 94 (21): 11333–8. Bibcode:1997PNAS...9411333H. doi:10.1073/pnas.94.21.11333. PMC 23459. PMID 9326610.

[pmid11741985-18] Roth W, Stenner-Liewen F, Pawlowski K, Godzik A, Reed JC (mart 2002). "Identification and characterization of DEDD2, a death effector domain-containing protein". J. Biol. Chem. 277 (9): 7501–8. doi:10.1074/jbc.M110749200. PMID 11741985.

[pmid8962078-19] ^ ^a ^b ^c ^d ^e ^f Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (decembar 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.

[pmid12232792-20] Cowling V, Downward J (oktobar 2002). "Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain". Cell Death Differ. 9 (10): 1046–56. doi:10.1038/sj.cdd.4401065. PMID 12232792.

[pmid11965497-21] Zhan Y, Hegde R, Srinivasula SM, Fernandes-Alnemri T, Alnemri ES (april 2002). "Death effector domain-containing proteins DEDD and FLAME-3 form nuclear complexes with the TFIIIC102 subunit of human transcription factor IIIC". Cell Death Differ. 9 (4): 439–47. doi:10.1038/sj.cdd.4401038. PMID 11965497.

[pmid12527898-22] Alcivar A, Hu S, Tang J, Yang X (januar 2003). "DEDD and DEDD2 associate with caspase-8/10 and signal cell death". Oncogene. 22 (2): 291–7. doi:10.1038/sj.onc.1206099. PMID 12527898.

[pmid9774341-23] Stegh AH, Schickling O, Ehret A, Scaffidi C, Peterhänsel C, Hofmann TG, Grummt I, Krammer PH, Peter ME (oktobar 1998). "DEDD, a novel death effector domain-containing protein, targeted to the nucleolus". EMBO J. 17 (20): 5974–86. doi:10.1093/emboj/17.20.5974. PMC 1170924. PMID 9774341.

[pmid19060883-24] 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 (februar 2009). "ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development". Nature. 457 (7231): 906–9. Bibcode:2009Natur.457..906O. doi:10.1038/nature07575. PMC 2642523. PMID 19060883.

[pmid12911633-25] Henshall DC, Araki T, Schindler CK, Shinoda S, Lan JQ, Simon RP (septembar 2003). "Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures". J. Neurochem. 86 (5): 1260–70. doi:10.1046/j.1471-4159.2003.01934.x. PMID 12911633. S2CID 21971958.

[pmid8681376-26] Boldin MP, Goncharov TM, Goltsev YV, Wallach D (juni 1996). "Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death". Cell. 85 (6): 803–15. doi:10.1016/s0092-8674(00)81265-9. PMID 8681376. S2CID 7415784.

[pmid12107169-27] Thomas LR, Stillman DJ, Thorburn A (septembar 2002). "Regulation of Fas-associated death domain interactions by the death effector domain identified by a modified reverse two-hybrid screen". J. Biol. Chem. 277 (37): 34343–8. doi:10.1074/jbc.M204169200. PMID 12107169.

[pmid9325248-28] MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES (oktobar 1997). "Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL". J. Biol. Chem. 272 (41): 25417–20. doi:10.1074/jbc.272.41.25417. PMID 9325248.

[pmid11788820-29] Gervais FG, Singaraja R, Xanthoudakis S, Gutekunst CA, Leavitt BR, Metzler M, Hackam AS, Tam J, Vaillancourt JP, Houtzager V, Rasper DM, Roy S, Hayden MR, Nicholson DW (februar 2002). "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nat. Cell Biol. 4 (2): 95–105. doi:10.1038/ncb735. PMID 11788820. S2CID 10439592.

[pmid9560245-30] Koseki T, Inohara N, Chen S, Núñez G (april 1998). "ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases". Proc. Natl. Acad. Sci. U.S.A. 95 (9): 5156–60. Bibcode:1998PNAS...95.5156K. doi:10.1073/pnas.95.9.5156. PMC 20230. PMID 9560245.

[pmid10493725-31] Kitsberg D, Formstecher E, Fauquet M, Kubes M, Cordier J, Canton B, Pan G, Rolli M, Glowinski J, Chneiweiss H (oktobar 1999). "Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis". J. Neurosci. 19 (19): 8244–51. doi:10.1523/JNEUROSCI.19-19-08244.1999. PMC 6783010. PMID 10493725.

[pmid10442631-32] Condorelli G, Vigliotta G, Cafieri A, Trencia A, Andalò P, Oriente F, Miele C, Caruso M, Formisano P, Beguinot F (august 1999). "PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis". Oncogene. 18 (31): 4409–15. doi:10.1038/sj.onc.1202831. PMID 10442631. S2CID 20510429.

[pmid11002417-33] Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (septembar 2000). "Activation of the NF-kappaB pathway by caspase 8 and its homologs". Oncogene. 19 (39): 4451–60. doi:10.1038/sj.onc.1203812. PMID 11002417.

[pmid18570872-34] Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ, Barker PA (juni 2008). "cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination". Mol. Cell. 30 (6): 689–700. doi:10.1016/j.molcel.2008.05.014. PMID 18570872.

[pmid11098060-35] Leo E, Deveraux QL, Buchholtz C, Welsh K, Matsuzawa S, Stennicke HR, Salvesen GS, Reed JC (mart 2001). "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". J. Biol. Chem. 276 (11): 8087–93. doi:10.1074/jbc.M009450200. PMID 11098060.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]