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6. აპოპტოზის ინჰიბიტორები
6. აპოპტოზის ინჰიბიტორები
inhibitor of apoptosis
Uujredis sikvdili - apoptozi da nekrozi
cIAP1 livini
cIAP2 NAIP
XIAP
misi geni 1.6 kb aris zomiT da akodirebs 31 kda cilas, romelsac gaaCnia
TuTiis TiTebis msgavsi motivi. Semdgomi kvlevebiT am ojaxSi daagjufes
is cilebi, romlebSic nanaxi iqna 1-dan 3-mde bakulovirusis IAP –is (BIR)
1
domenebi N-kidra aminoboloze. zogierT IAP-s aseve aqvs RING (really interesting
new gene ) TiTebis domeni C-kidura boloze.
2
apoptozuri cilis
X-dakavSirebuli inhibitori
adamianis apoptozis
inhibitori cila-1
adamianis apoptozis
inhibitori cila -2
neironuli apoptozis
inhibitoruli cila
survivini
livini
1)Sida-mitoqondriuli gza;
3
XIAP aris erT-erTi yvelze kargad daxasiaTebuli inhibitori. Xiap (X-Linked
Inhibitor of Apoptosis Protein ) Sedgeba 498 aminomJa-visagan (~55 kDa) igi iTvleba
yvelaze Zlier endogenur inhibitorad. Mmas aqvs 3 BIR domeni: BIR1, BIR2 da
BIR3, romlebic gamoirCevian kaspazebisadmi maRali aqtiobiT, magram
araerTnairi funqciiT. D BIR2 domeni da BIR1–isa da BIR2–is damakavSirebeli
regioni specifiurad ukavSirdeba da ainhibi-rebs kaspaza3-s da kaspaza-7-s.
BIR2 domeni Tavsdeba kaspaza3-is aqtiur saitTan da mis aqtiobas ainhibirebs
substratis-damakavSirebeli jibis blokirebiT. BIR1-2 fragmentis
zeeqspresia mniSvnelovan rols TamaSobs Fas/kaspaza-8-iT ganpirobebul
apoptozSi. Kkaspaza-9-is inhibirebisaTvis IAP saWiroebs rogorc BIR3 aseve
RING domens.
4
endoplazmuri badis stresiT gamowveuli apoptozuri gzis dros, IAPs
ainhibireben kaspaza-2-s da kaspaza-9-s maTi BIR domenis dakavSirebiT.
endoplazmuri badis roli gansakuT-rebiT kritikulia rogorc gare, ise
Sida apoptozur gzaSi. kaspaza-2, romelic lokalizebulia endoplazmur
retikulum-ze, kaspaza-9-sTan erTad warmoadgens er-is stresiT gamowve-
uli apoptozis mediators. isini aaqtiveben kaspaza 3-s da 7-s. miuxedavad
imisa, rom zog IAPs –s SeuZlia kaspaza 3,7,da 9-is dakavSireba da inhibireba,
mxolod ujreduli IAP 2 (c-IAP2) ukavSirdeba kaspaza2-s uSualod BIR2
domeniT da ainhibirebs mas.
5
giganturi BIR domenis Semcveli cila BRUCE aris IAP ojaxis unikaluri
wevri, romelic ormagi roliT aris cno-bili. Mmis N-kidura BIR domens
SeuZlia substratTan dakav-Sireba, xolo C-kidura UBC domeni
uzrunvelyofs E2 aqtio-bas. BRUCE-s aqvs araCveulebrivi sistema
ubiqvitiniT koni-ugirebisaTvis. aq erT polipeptidSi axdens E2/E3
aqtiobebis gaerTianebas da miiReba qimeuli E2/E3 ligaza. autoubi-
qvitinirebiT zogierTi IAPs negatiurad aregulirebs Tavis Tavs. es
procesi inhibitoris degradirebasa da apoptozis progresirebas iwvevs.
6
Semdeg Smac/DIABLO da HtrA2/Omi ixliCebian da Rebuloben TavianT aqtiur
formas: TaRis magvar dimers da piramidis magvar homotrimers Sesabamisad.