Apoptosis Modulation and Signaling (Homo sapiens)

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21DNAApoptotic factors"Amplification loop"Modulation of apoptosisApoptosomeTRAFsPIDDosomeDNA-FragmentationActivation of Caspases- extrinsic pathwayMitochondriaMIR29B1Ca2+JNKC-IAP2IL1R1AP-1IKB-alphaDAXXsurvivinBFL-1CASP2APAF1BOKIKKBimBAXTOLLIPOsteoprotegerinIL1R2MADDc-FLIPAIFM1TRADDFasLTRAF6CASP3TRADDCASP4NIKDR3ERKMYD88CASP6TNFR-2CASP2CRADDARTSCASP9CASP1p16-INK4BLKBAG3HSPA1APIDDApollonBIKCyto CAsk1BADBcl-WAP-1BIDTP53CASP7JNKTNFR-1HRKPRKD1c-FLIPHumaninNAIPXIAPCalpainAIFM2TNFR-1IL1R1MCL1BMFDR3DcR3Bit1RIPK1FAP-1TRAIL-R1ENDOGCASP2TRAILBAK1HTRA2/OmiDFFABNIP3SurvivinPEA15CASP10c-fosBcl-BFADDDFFBFASCASP8TRAIL-R4BCL2CASP8Smac/DIABLOIRAK1IG20Nf-kBTRAIL-R2RIPK1BCL-XLTNFR-1TRAF3Bcl-XsC-IAP1TRADDLivinFASPumaTRAIL-R3NoxaThe interactions of this pathway were computationally validated. See reference.DISCActivation of Caspases- intrinsic pathwayMIR29B2


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".


GenMAPP notes 
Rückert F et al. Examination of Apoptosis Signaling in Pancreatic Cancer by Computational Signal Transduction Analysis.

PLoS ONE, 2010. 5: e12243

GenMAPP remarks 
Arrows: activation, broken arrows: inhibtion

Quality Tags

Ontology Terms



  1. Mott JL, Kobayashi S, Bronk SF, Gores GJ; ''mir-29 regulates Mcl-1 protein expression and apoptosis.''; Oncogene, 2007 PubMed
  2. Rückert F, Dawelbait G, Winter C, Hartmann A, Denz A, Ammerpohl O, Schroeder M, Schackert HK, Sipos B, Klöppel G, Kalthoff H, Saeger HD, Pilarsky C, Grأ¼tzmann R; ''Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.''; PLoS One, 2010 PubMed


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94912view00:04, 13 October 2017Khanspersremoved unconnected line
94749view15:19, 5 October 2017Ryanmillerconnected lines
91293view21:56, 23 January 2017AlexanderPicoRemoved old genmapp info
88979view09:23, 18 August 2016MirellaKalafatiOntology Term : 'regulatory pathway' added !
88897view07:49, 17 August 2016MirellaKalafatiOntology Term : 'signaling pathway' added !
87370view09:56, 22 July 2016MaintBotadded missing graphids
85184view14:34, 23 April 2016EgonwFixed weird chars in references.
85183view14:32, 23 April 2016EgonwReplaced a mim-conversion with Arrow.
84701view21:23, 15 March 2016KhanspersQuick edit to datanode annotation or property
80459view21:52, 24 June 2015KhanspersReverted to version '19:01, 14 May 2015' by Khanspers
80449view18:11, 23 June 2015KhanspersAdded mir29a,c targeting of MCL1 and BCL2
80152view19:01, 14 May 2015KhanspersAdded mir29b targeting and associated lit ref, cleaned up interactions, added Ca2+ metabolite
80004view09:39, 30 April 2015ZariCorrected ID for AIFM1,CASP4,CASP2,CASP1,HSPA1A,PIDD,TP53,PRKD1,NAIP,XIAP,AIFM2,RIPK1 and PEA15 genes
79833view09:37, 17 April 2015EgonwFixed the data source to HGNC.
63162view20:24, 8 May 2013MaintBotUpdating GPML version
44957view12:39, 6 October 2011MartijnVanIerselOntology Term : 'apoptotic cell death pathway' added !
42308view17:21, 16 March 2011KhanspersReverted to version '23:30, 1 March 2011' by Khanspers
42307view16:56, 15 March 2011Frances55Apoptosis Modulation and Signaling (Homo sapiens
41111view23:30, 1 March 2011Khanspers
40443view22:59, 25 February 2011Khansperstest
39652view13:15, 7 January 2011Felix555Design
39651view13:14, 7 January 2011Felix555Modified categories
39624view19:39, 4 January 2011KhanspersModified categories
39608view13:01, 30 December 2010Felix555New design
39607view12:53, 30 December 2010Felix555New design
39606view12:42, 30 December 2010Felix555Database connotations
39604view11:31, 30 December 2010Felix555Periodical save, work in progress
39603view11:09, 30 December 2010Felix555Periodical save, work in progress
39596view13:55, 29 December 2010Felix555Specify description
39595view13:54, 29 December 2010Felix555Bibliography
39594view13:49, 29 December 2010Felix555Modified description
39593view13:48, 29 December 2010Felix555...
39592view13:47, 29 December 2010Felix555New pathway

External references


View all...
NameTypeDatabase referenceComment
AIFM1GeneProduct9131 (Entrez Gene)
AIFM2GeneProduct84883 (Entrez Gene)
AP-1GeneProductJUN (HGNC)
APAF1GeneProductAPAF1 (HGNC)
ApollonGeneProductBIRC6 (HGNC)
Ask1GeneProductMAP3K5 (HGNC)
BADGeneProductBAD (HGNC)
BAG3GeneProductBAG3 (HGNC)
BAK1GeneProductBAK1 (HGNC)
BAXGeneProductBAX (HGNC)
BCL-XLGeneProductBCL2L1 (HGNC)
BCL2GeneProductBCL2 (HGNC)
BFL-1GeneProductBCL2A1 (HGNC)
BIDGeneProductBID (HGNC)
BIKGeneProductBIK (HGNC)
BLKGeneProductBLK (HGNC)
BMFGeneProductBMF (HGNC)
BNIP3GeneProductBNIP3 (HGNC)
BOKGeneProductBOK (HGNC)
Bcl-BGeneProductBCL2L10 (HGNC)
Bcl-WGeneProductBCL2L2 (HGNC)
Bcl-XsGeneProductBCL2L1 (HGNC)
BimGeneProductBCL2L11 (HGNC)
Bit1GeneProductPTRH2 (HGNC)
C-IAP1GeneProductBIRC2 (HGNC)
C-IAP2GeneProductBIRC3 (HGNC)
CASP10GeneProductCASP10 (HGNC)
CASP1GeneProduct834 (Entrez Gene)
CASP2GeneProduct1503 (HGNC)
CASP2GeneProduct835 (Entrez Gene)
CASP2GeneProductCASP2 (HGNC)
CASP3GeneProductCASP3 (HGNC)
CASP4GeneProduct837 (Entrez Gene)
CASP6GeneProductCASP6 (HGNC)
CASP7GeneProductCASP7 (HGNC)
CASP8GeneProductCASP8 (HGNC)
CASP9GeneProductCASP9 (HGNC)
Ca2+MetaboliteHMDB00464 (HMDB)
CalpainGeneProductCAPNS1 (HGNC)
Cyto CGeneProductCYCS (HGNC)
DR3GeneProductTNFRSF25 (HGNC)
DcR3GeneProductTNFRSF6B (HGNC)
ERKGeneProductMAPK3 (HGNC)
FAP-1GeneProductPTPN13 (HGNC)
FASGeneProductFAS (HGNC)
FasLGeneProductFASLG (HGNC)
HRKGeneProductHRK (HGNC)
HSPA1AGeneProduct3303 (Entrez Gene)
HTRA2/OmiGeneProductHTRA2 (HGNC)
HumaninGeneProductHN1 (HGNC)
IG20GeneProductMADD (HGNC)
IKB-alphaGeneProductNFKBIA (HGNC)
IL1R1GeneProductIL1R1 (HGNC)
IL1R2GeneProductIL1R2 (HGNC)
IRAK1GeneProductIRAK1 (HGNC)
JNKGeneProductMAPK8 (HGNC)
LivinGeneProductBIRC7 (HGNC)
MCL1GeneProductMCL1 (HGNC)
MIR29B1GeneProductENSG00000274250 (Ensembl)
MIR29B2GeneProductENSG00000276752 (Ensembl)
MYD88GeneProductMYD88 (HGNC)
NAIPGeneProduct4671 (Entrez Gene)
NIKGeneProductMAP3K14 (HGNC)
Nf-kBGeneProductNFKB1 (HGNC)
NoxaGeneProductPMAIP1 (HGNC)
OsteoprotegerinGeneProductTNFRSF11B (HGNC)
PEA15GeneProduct8682 (Entrez Gene)
PIDDGeneProduct55367 (Entrez Gene)
PRKD1GeneProduct5587 (Entrez Gene)
PumaGeneProductBBC3 (HGNC)
RIPK1GeneProduct8737 (Entrez Gene)
SurvivinGeneProductBIRC5 (HGNC)
TP53GeneProduct7157 (Entrez Gene)
TRAF3GeneProductTRAF3 (HGNC)
TRAF6GeneProductTRAF6 (HGNC)
XIAPGeneProduct331 (Entrez Gene)
c-fosGeneProductFOS (HGNC)
p16-INK4GeneProductCDKN2A (HGNC)
survivinGeneProductBIRC5 (HGNC)

Annotated Interactions

No annotated interactions
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