description
Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of "cell-death", and the mechanisms of various apoptotic pathways are still being revealed today. The two principal pathways of apoptosis are (1) the Bcl-2 inhibitable or intrinsic pathway induced by various forms of stress like intracellular damage, developmental cues, and external stimuli and (2) the caspase 8/10 dependent or extrinsic pathway initiated by the engagement of death receptors The caspase 8/10 dependent or extrinsic pathway is a death receptor mediated mechanism that results in the activation of caspase-8 and caspase-10. Activation of death receptors like Fas/CD95, TNFR1, and the TRAIL receptor is promoted by the TNF family of ligands including FASL (APO1L OR CD95L), TNF, LT-alpha, LT-beta, CD40L, LIGHT, RANKL, BLYS/BAFF, and APO2L/TRAIL. These ligands are released in response to microbial infection, or as part of the cellular, humoral immunity responses during the formation of lymphoid organs, activation of dendritic cells, stimulation or survival of T, B, and natural killer (NK) cells, cytotoxic response to viral infection or oncogenic transformation. The Bcl-2 inhibitable or intrinsic pathway of apoptosis is a stress-inducible process, and acts through the activation of caspase-9 via Apaf-1 and cytochrome c. The rupture of the mitochondrial membrane, a rapid process involving some of the Bcl-2 family proteins, releases these molecules into the cytoplasm. Examples of cellular processes that may induce the intrinsic pathway in response to various damage signals include: auto reactivity in lymphocytes, cytokine deprivation, calcium flux or cellular damage by cytotoxic drugs like taxol, deprivation of nutrients like glucose and growth factors like EGF, anoikis, transactivation of target genes by tumor suppressors including p53. In many non-immune cells, death signals initiated by the extrinsic pathway are amplified by connections to the intrinsic pathway. The connecting link appears to be the truncated BID (tBID) protein a proteolytic cleavage product mediated by caspase-8 or other enzymes

external resources
NCBI:83060
KEGG:hsa04210
NCBI:1270262
REACTOME:R-HSA-109581
PUBMED:12189384
PUBMED:20533903
PUBMED:18208375
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PUBMED:19148180
PUBMED:16397578
PUBMED:15719025
PUBMED:15322527
PUBMED:15725726
PUBMED:12209154
PUBMED:23803157

genes
ACTB , ACTG1 , PARP1 , PARP4 , AKT1 , AKT2 , APAF1 , BIRC2 , BIRC3 , XIAP , BIRC5 , FAS , FASLG , ATF4 , ATM , BAD , BAK1 , BAX , BCL2 , BCL2A1 , BCL2L1 , BID , CAPN1 , CAPN2 , CASP2 , CASP3 , CASP6 , CASP7 , CASP8 , CASP9 , CASP10 , CTSC , CHUK , CSF2RB , CTSB , CTSD , CTSH , CTSK , CTSL , CTSV , CTSO , CTSS , CTSW , CTSZ , DAXX , GADD45A , DDIT3 , DFFA , DFFB , EIF2S1 , ENDOG , ERN1 , FOS , GZMB , HRAS , IKBKB , IL3 , IL3RA , ITPR1 , ITPR2 , ITPR3 , JUN , KRAS , LMNA , LMNB1 , MCL1 , MAP3K5 , GADD45B , NFKB1 , NFKBIA , NGF , NRAS , NTRK1 , PDPK1 , PIK3CA , PIK3CB , PIK3CD , PIK3R1 , PIK3R2 , PMAIP1 , SEPT4 , PRF1 , MAPK1 , MAPK3 , MAPK8 , MAPK9 , MAPK10 , MAP2K1 , MAP2K2 , PTPN13 , RAF1 , RELA , SPTA1 , SPTAN1 , TNF , TNFRSF1A , TP53 , TRAF1 , TRAF2 , TUBA4A , TUBA3C , TUBA1A , PIK3R3 , IKBKG , TRADD , CTSF , RIPK1 , HRK , TNFSF10 , FADD , TNFRSF10D , TNFRSF10C , TNFRSF10B , TNFRSF10A , CFLAR , MAP3K14 , AIFM1 , EIF2AK3 , AKT3 , BCL2L11 , PARP2 , PARP3 , TUBA1B , GADD45G , BBC3 , HTRA2 , TUBA8 , CYCS , PIDD1 , DIABLO , TP53AIP1 , TUBAL3 , TUBA1C , LMNB2 , TUBA3E , TUBA3D , DAB2IP , CASP12 , ADD1 , APC , BMX , CD14 , CDH1 , CTNNB1 , DAPK1 , DAPK3 , DCC , DSG1 , DSG2 , DSG3 , DSP , E2F1 , FNTA , GAS2 , SFN , GSN , H1F0 , HIST1H1C , HIST1H1D , HIST1H1E , HIST1H1B , HIST1H1A , HMGB1 , HMGB2 , KPNA1 , KPNB1 , MAPT , NMT1 , OPA1 , PAK2 , PKP1 , PLEC , PPP3CC , PPP3R1 , PRKCD , PRKCQ , PSMA1 , PSMA2 , PSMA3 , PSMA4 , PSMA5 , PSMA6 , PSMA7 , PSMB1 , PSMB2 , PSMB3 , PSMB4 , PSMB5 , PSMB6 , PSMB7 , PSMB8 , PSMB9 , PSMB10 , PSMC1 , PSMC2 , PSMC3 , PSMC4 , PSMC5 , PSMC6 , PSMD1 , PSMD2 , PSMD3 , PSMD4 , PSMD5 , PSMD7 , PSMD8 , PSMD9 , PSMD10 , PSMD11 , PSMD12 , PSMD13 , PSME1 , PSME2 , PTK2 , ROCK1 , RPS27A , SATB1 , TFDP1 , TFDP2 , TJP1 , TLR3 , TLR4 , TP53BP2 , TP73 , UBA52 , UBB , UBC , VIM , YWHAB , YWHAE , YWHAG , YWHAH , YWHAZ , SEM1 , STK24 , TP63 , DYNLL1 , TJP2 , PSMF1 , MAGED1 , PSMD6 , DNM1L , BCAP31 , PSME3 , PSMD14 , YWHAQ , ACIN1 , PSME4 , PPP1R13B , DAPK2 , LY96 , APPL1 , DBNL , STK26 , CLSPN , ARHGAP10 , UNC5A , BMF , OMA1 , PSMB11 , DYNLL2 , PSMA8 , TICAM1 , UNC5B , TICAM2 , C7orf76 , MIR637 , MIR3191 , LOC100506136 , OCLN ,