p53 signaling pathway - Homo sapiens (human)

Curator(s): Joe Strothman

p53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated genes. This results in three major outputs; cell cycle arrest, cellular senescence or apoptosis. Other p53-regulated gene functions communicate with adjacent cells, repair the damaged DNA or set up positive and negative feedback loops that enhance or attenuate the functions of the p53 protein and integrate these stress responses with other signal transduction pathways.    
Zoom out 50% Move left to zoom out, right to zoom in Zoom in 50% 100%

p53 signaling pathway - Homo sapiens (human) cluster_node46 Stress signals cluster_node47 !m cluster_node48 Target genes cluster_node49 !sic cluster_Mitochondrion Mitochondrion cluster_Response Response ataxia telangiectasia mutated ATM CHK2 ATM->CHK2 +p ataxia telangiectasia and Rad3 related ATR CHK1 ATR->CHK1 +p p53 ATR->p53 +p CHK2->p53 +p CHK1->p53 +p pl4ARF Mdm2 p53 binding protein homolog (mouse) MDM2 pl4ARF->MDM2 node1 2 MDM2->node1 MDM2 MDM2->p53 node2 MDM-X MDM2->node2 node3 10 p53->MDM2 p53->node3 p53 DNA p53->DNA node19 1 DNA->node19 node20 2 DNA->node20 node21 3 DNA->node21 node15 ? DNA->node15 BCL2-associated X protein BAX DNA->BAX node12 IGF-BP3 DNA->node12 MDM2 2 DNA->MDM2 2 P48 DNA->P48 PAI DNA->PAI phosphatidylinositol glycan anchor biosynthesis,class S PIGS DNA->PIGS phosphatase and tensin homolog PTEN DNA->PTEN Scotin DNA->Scotin TSAP6 DNA->TSAP6 p21 DNA->p21 node6 1 node8 1 node9 1 node10 16 node11 1 node13 2 node14 2 node16 10 node17 Cyclin D CDK4/6 node17->node16 Cyclin D~CDK4/6 node22 4 node17->node22 node18 Cyclin E CDK2 node18->node22 node7 14-3 -3-o node19->node7 Reprimo node19->Reprimo B99 node20->B99 Gadd45 node20->Gadd45 Fas (TNF receptor superfamily,member 6) FAS node21->FAS p53-induced death domain protein PIDD node21->PIDD node32 G1 arrest (sustained) node22->node32 node23 3 node24 Cyclin B Cdc2 node24->node23 Cyclin B~Cdc2 node33 G2 arrest (sustained) node24->node33 node25 3 DR5 DR5->node25 DR5 caspase 8,apoptosis-related cysteine peptidase CASP8 DR5->CASP8 node26 6 CASP8->node26 CASP8 BH3 interacting domain death agonist BID CASP8->BID caspase 3,apoptosis-related cysteine peptidase CASP3 CASP8->CASP3 tBid BID->tBid node27 2 CytC CytC->node27 CytC caspase 9,apoptosis-related cysteine peptidase CASP9 CytC->CASP9 node28 Apaf-1 node28->CASP9 node29 9 CASP9->node29 CASP9 CASP9->CASP3 node30 26 CASP3->node30 CASP3 Apoptosis CASP3->Apoptosis Noxa PUMA Noxa->PUMA P53AIP PUMA->P53AIP P53AIP->tBid node31 1 ROS ROS->node31 ROS ROS->tBid PERP,TP53 apoptosis effector PERP PAG608 PERP->PAG608 Siah PAG608->Siah Siah->tBid Cell cycle arrest node32->Cell cycle arrest node33->Cell cycle arrest node34 2 IGF IGF->node34 IGF IGF->Apoptosis brain-specific angiogenesis inhibitor 1 BAI1 KAI BAI1->KAI node35 GD-AiF KAI->node35 TSP1 node35->TSP1 Maspin TSP1->Maspin Inhibition of angiogenesis and metastasis Maspin->Inhibition of angiogenesis and metastasis p53R2 Gadd45 2 p53R2->Gadd45 2 node36 1 Gadd45 2->node36 Gadd45 2 Sestrins Gadd45 2->Sestrins DNA repair and damage prevention Sestrins->DNA repair and damage prevention node38 1 tuberous sclerosis 2 TSC2 TSC2->node38 TSC2 node40 IGF-BP3 2 TSC2->node40 node39 1 node40->node39 IGF-BP3 2 node37 Inhibition of IGF-1/mTOR pathway node40->node37 node41 Cop-1 node42 PIRH-2 node41->node42 Cyclin G node42->Cyclin G node43 Siah-1 Cyclin G->node43 Wip1 node43->Wip1 deltaNp73 Wip1->deltaNp73 p53 negative feedback deltaNp73->p53 negative feedback node44 5 Hypoxia node44->Hypoxia Nitric Oxide node44->Nitric Oxide node45 6 node45->Nitric Oxide node4 Oncogene Activation (Such as MYC, E2F1, Ras, BCR-ABL) node45->node4 node7->node24 Gadd45->node8 Gadd45 Gadd45->node24 FAS->node9 FAS FAS->DR5 PIDD->DR5 Hypoxia->p53 Nitric Oxide->p53 node4->pl4ARF Cellular senescence node15->Cellular senescence BAX->node10 BAX BAX->Noxa tBid->CytC node12->node11 IGF-BP3 node12->IGF MDM2 2->node14 MDM2 2 MDM2 2->node41 P48->p53R2 PAI->BAI1 PIGS->ROS PTEN->node13 PTEN PTEN->TSC2 Scotin->PERP Exosome mediated secretion TSAP6->Exosome mediated secretion p21->node6 p21 p21->node17 p21->node18 DNA damage 1 DNA damage 1->ATM DNA damage 1->ATR Gamma irradiation Gamma irradiation->DNA damage 1 Genotoxic drugs Genotoxic drugs->DNA damage 1 node5 Heat / Cold Shock node5->node45 node2->MDM2 node2->p53 Nutrition deprivation Nutrition deprivation->node44 UV UV->DNA damage 1 Cell cycle 1 print "