Apoptosis Modulation and Signaling (Homo sapiens)

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DNA Apoptotic factors "Amplification loop" Modulation of apoptosis Apoptosome TRAFs PIDDosome DNA-Fragmentation Activation of Caspases- extrinsic pathway Mitochondria JNK Ca2+ MIR29B1 MIR29B2 C-IAP2 IL1R1 AP-1 IKB-alpha DAXX survivin BFL-1 CASP2 CASP3 CASP7 APAF1 BOK IKK Bim BAX TOLLIP Osteoprotegerin IL1R2 MADD c-FLIP AIFM1 TRADD FasL TRAF6 TRADD CASP4 NIK DR3 ERK MYD88 CASP6 TNFR-2 CASP2 CRADD ARTS CASP9 CASP1 p16-INK4 BLK BAG3 HSPA1A PIDD Apollon BIK Cyto C Ask1 BAD Bcl-W AP-1 BID TP53 JNK TNFR-1 HRK PRKD1 c-FLIP Humanin NAIP XIAP Calpain AIFM2 TNFR-1 IL1R1 MCL1 BMF DR3 DcR3 Bit1 RIPK1 FAP-1 TRAIL-R1 ENDOG CASP2 TRAIL BAK1 HTRA2/Omi DFFA BNIP3 Survivin PEA15 CASP10 c-fos Bcl-B FADD DFFB FAS CASP8 TRAIL-R4 BCL2 CASP8 Smac/DIABLO IRAK1 IG20 Nf-kB TRAIL-R2 RIPK1 BCL-XL TNFR-1 TRAF3 Bcl-Xs C-IAP1 TRADD Livin FAS Puma TRAIL-R3 Noxa The interactions of this pathway were computationally validated. See reference. DISC Activation of Caspases- intrinsic pathway Name: Apoptosis Modulation and Signaling License: CC BY 2.0 Organism: 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".

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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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94912view 17:04, 12 October 2017Khanspersremoved unconnected line
94749view 08:19, 5 October 2017Ryanmillerconnected lines
91293view 14:56, 23 January 2017AlexanderPicoRemoved old genmapp info
88979view 02:23, 18 August 2016MirellaKalafatiOntology Term : 'regulatory pathway' added !
88897view 00:49, 17 August 2016MirellaKalafatiOntology Term : 'signaling pathway' added !
87370view 02:56, 22 July 2016MaintBotadded missing graphids
85184view 07:34, 23 April 2016EgonwFixed weird chars in references.
85183view 07:32, 23 April 2016EgonwReplaced a mim-conversion with Arrow.
84701view 14:23, 15 March 2016KhanspersQuick edit to datanode annotation or property
80459view 14:52, 24 June 2015KhanspersReverted to version '19:01, 14 May 2015' by Khanspers
80449view 11:11, 23 June 2015KhanspersAdded mir29a,c targeting of MCL1 and BCL2
80152view 12:01, 14 May 2015KhanspersAdded mir29b targeting and associated lit ref, cleaned up interactions, added Ca2+ metabolite
80004view 02:39, 30 April 2015ZariCorrected ID for AIFM1,CASP4,CASP2,CASP1,HSPA1A,PIDD,TP53,PRKD1,NAIP,XIAP,AIFM2,RIPK1 and PEA15 genes
79833view 02:37, 17 April 2015EgonwFixed the data source to HGNC.
63162view 13:24, 8 May 2013MaintBotUpdating GPML version
44957view 05:39, 6 October 2011MartijnVanIerselOntology Term : 'apoptotic cell death pathway' added !
42308view 10:21, 16 March 2011KhanspersReverted to version '23:30, 1 March 2011' by Khanspers
42307view 09:56, 15 March 2011Frances55Apoptosis Modulation and Signaling (Homo sapiens
41111view 16:30, 1 March 2011Khanspers
40443view 15:59, 25 February 2011Khansperstest
39652view 06:15, 7 January 2011Felix555Design
39651view 06:14, 7 January 2011Felix555Modified categories
39624view 12:39, 4 January 2011KhanspersModified categories
39608view 06:01, 30 December 2010Felix555New design
39607view 05:53, 30 December 2010Felix555New design
39606view 05:42, 30 December 2010Felix555Database connotations
39604view 04:31, 30 December 2010Felix555Periodical save, work in progress
39603view 04:09, 30 December 2010Felix555Periodical save, work in progress
39596view 06:55, 29 December 2010Felix555Specify description
39595view 06:54, 29 December 2010Felix555Bibliography
39594view 06:49, 29 December 2010Felix555Modified description
39593view 06:48, 29 December 2010Felix555...
39592view 06:47, 29 December 2010Felix555New pathway

External references


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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

<cite>No annotated interactions</cite>