Apoptosis modulation and signaling (WP1772)

Homo sapiens

Apoptosis, or cell death program, can be activated by various mechanisms within the extrinsic and the intrinsic pathway. While activation of cell death receptors leads to the engagement of the extrinsic pathway, the intrinsic pathway is activated by mitochondria during cellular stress, both resulting in an activation of caspases. In the present pathway we emphasized the activation of caspases by those two pathways in pancreatic cancer (PDAC) cells. Please notice, that PDAC cells are so called type-II cells. In these cells the activation of cell death receptors is not sufficient to activated caspases. By cleavage of Bid, type-II cells activate the intrinsic pathway as "amplification loop". Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP1772 CPTAC Assay Portal]


Felix Rckert , Kristina Hanspers , Frances , Martijn Van Iersel , Egon Willighagen , Zahra Roudbari , Marianthi Kalafati , Alex Pico , Ryan Miller , Marvin Martens , Friederike Ehrhart , Anders Riutta , Daniel Domingo-Fdez , and Eric Weitz


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Homo sapiens



Pathway Ontology

regulatory pathway signaling pathway apoptotic cell death pathway


Label Type Compact URI Comment
Ca2+ Metabolite hmdb:HMDB0000464
JNK GeneProduct hgnc.symbol:MAPK8
MIR29B1 GeneProduct ensembl:ENSG00000283797
BIRC3 GeneProduct hgnc.symbol:BIRC3
IL1R1 GeneProduct hgnc.symbol:IL1R1
JUN GeneProduct hgnc.symbol:JUN
NFKBIA GeneProduct hgnc.symbol:NFKBIA
DAXX GeneProduct hgnc.symbol:DAXX
BIRC5 GeneProduct ensembl:ENSG00000089685
BCL2A1 GeneProduct hgnc.symbol:BCL2A1
CASP2 GeneProduct ncbigene:835
APAF1 GeneProduct hgnc.symbol:APAF1
BOK GeneProduct hgnc.symbol:BOK
IKK GeneProduct hgnc.symbol:IKBKB
BCL2L11 GeneProduct ensembl:ENSG00000153094
BAX GeneProduct hgnc.symbol:BAX
TOLLIP GeneProduct hgnc.symbol:TOLLIP
TNFRSF11B GeneProduct hgnc.symbol:ENSG00000164761
IL1R2 GeneProduct hgnc.symbol:IL1R2
MADD GeneProduct hgnc.symbol:MADD
CFLAR GeneProduct hgnc.symbol:CFLAR
AIFM1 GeneProduct ncbigene:9131
TRADD GeneProduct hgnc.symbol:TRADD
FASLG GeneProduct hgnc.symbol:FASLG
TRAF6 GeneProduct hgnc.symbol:TRAF6
CASP3 GeneProduct hgnc.symbol:CASP3
TRADD GeneProduct hgnc.symbol:TRADD
CASP4 GeneProduct ncbigene:837
NIK GeneProduct hgnc.symbol:MAP3K14
TNFRSF25 GeneProduct hgnc.symbol:TNFRSF25
ERK GeneProduct hgnc.symbol:MAPK3
MYD88 GeneProduct hgnc.symbol:MYD88
CASP6 GeneProduct hgnc.symbol:CASP6
TNFRSF1B GeneProduct hgnc.symbol:TNFRSF1B
CASP2 GeneProduct hgnc:1503
CRADD GeneProduct hgnc.symbol:CRADD
SEPTIN4 GeneProduct ensembl:ENSG00000108387
CASP9 GeneProduct hgnc.symbol:CASP9
CASP1 GeneProduct ncbigene:834
CDKN2A GeneProduct hgnc.symbol:CDKN2A
BLK GeneProduct hgnc.symbol:BLK
BAG3 GeneProduct hgnc.symbol:BAG3
HSPA1A GeneProduct ncbigene:3303
PIDD GeneProduct ncbigene:55367
BIRC6 GeneProduct hgnc.symbol:ENSG00000115760
BIK GeneProduct hgnc.symbol:BIK
CYCS GeneProduct ensembl:ENSG00000172115
MAP3K5 GeneProduct hgnc.symbol:MAP3K5
BAD GeneProduct hgnc.symbol:BAD
BCL2L2 GeneProduct hgnc.symbol:BCL2L2
JUN GeneProduct hgnc.symbol:JUN
BID GeneProduct hgnc.symbol:BID
TP53 GeneProduct ncbigene:7157
CASP7 GeneProduct hgnc.symbol:CASP7
JNK GeneProduct hgnc.symbol:MAPK8
TNFRSF1A GeneProduct hgnc.symbol:TNFRSF1A
HRK GeneProduct hgnc.symbol:HRK
PRKD1 GeneProduct ncbigene:5587
CFLAR GeneProduct hgnc.symbol:CFLAR
MT-RNR2 GeneProduct ensembl:ENSG00000210082
NAIP GeneProduct ncbigene:4671
XIAP GeneProduct ncbigene:331
CAPNS1 GeneProduct hgnc.symbol:CAPNS1
AIFM2 GeneProduct ncbigene:84883
TNFRSF1A GeneProduct hgnc.symbol:TNFRSF1A
IL1R1 GeneProduct hgnc.symbol:IL1R1
MCL1 GeneProduct hgnc.symbol:MCL1
BMF GeneProduct hgnc.symbol:BMF
TNFRSF25 GeneProduct hgnc.symbol:TNFRSF25
TNFRSF6B GeneProduct hgnc.symbol:TNFRSF6B
PTRH2 GeneProduct ensembl:ENSG00000141378
RIPK1 GeneProduct ncbigene:8737
PTPN13 GeneProduct ensembl:ENSG00000163629
TNFRSF10A GeneProduct ensembl:ENSG00000104689
ENDOG GeneProduct hgnc.symbol:ENDOG
CASP2 GeneProduct hgnc.symbol:CASP2
TNFSF10 GeneProduct ensembl:ENSG00000121858
BAK1 GeneProduct hgnc.symbol:BAK1
HTRA2 GeneProduct ensembl:ENSG00000115317
DFFA GeneProduct hgnc.symbol:DFFA
BNIP3 GeneProduct hgnc.symbol:BNIP3
BIRC5 GeneProduct ensembl:ENSG00000089685
PEA15 GeneProduct ncbigene:8682
CASP10 GeneProduct hgnc.symbol:CASP10
FOS GeneProduct hgnc.symbol:FOS
BCL2L10 GeneProduct hgnc.symbol:BCL2L10
FADD GeneProduct hgnc.symbol:FADD
DFFB GeneProduct hgnc.symbol:DFFB
FAS GeneProduct hgnc.symbol:FAS
CASP8 GeneProduct hgnc.symbol:CASP8
TNFRSF10D GeneProduct ensembl:ENSG00000173530
BCL2 GeneProduct hgnc.symbol:BCL2
CASP8 GeneProduct hgnc.symbol:CASP8
DIABLO GeneProduct ensembl:ENSG00000184047
IRAK1 GeneProduct hgnc.symbol:IRAK1
IG20 GeneProduct ensembl:ENSG00000110514
NFKB1 GeneProduct hgnc.symbol:NFKB1
TNFRSF10B GeneProduct ensembl:ENSG00000120889
RIPK1 GeneProduct ncbigene:8737
BCL-XL GeneProduct hgnc.symbol:BCL2L1
TNFRSF1A GeneProduct hgnc.symbol:TNFRSF1A
TRAF3 GeneProduct hgnc.symbol:TRAF3
BCL2L1 GeneProduct hgnc.symbol:ENSG00000171552
BIRC2 GeneProduct hgnc.symbol:BIRC2
TRADD GeneProduct hgnc.symbol:TRADD
BIRC7 GeneProduct ensembl:ENSG00000101197
FAS GeneProduct hgnc.symbol:FAS
BBC3 GeneProduct ensembl:ENSG00000105327
TNFRSF10C GeneProduct ensembl:ENSG00000173535
PMAIP1 GeneProduct ensembl:ENSG00000141682
MIR29B2 GeneProduct ensembl:ENSG00000284203


  1. mir-29 regulates Mcl-1 protein expression and apoptosis. Mott JL, Kobayashi S, Bronk SF, Gores GJ. Oncogene. 2007 Sep 13;26(42):6133–40. PubMed Europe PMC Scholia
  2. Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis. Rückert F, Dawelbait G, Winter C, Hartmann A, Denz A, Ammerpohl O, et al. PLoS One. 2010 Aug 19;5(8):e12243. PubMed Europe PMC Scholia