The p53 pathway responds to stresses that can disrupt the fidelity of DNA replication and cell division. A stress signal is transmitted to the p53 protein by post-translational modifications. This results in the activation of the p53 protein as a transcription factor that initiates a program of cell cycle arrest, cellular senescence or apoptosis. The transcriptional network of p53-responsive genes produces proteins that interact with a large number of other signal transduction pathways in the cell and a number of positive and negative autoregulatory feedback loops act upon the p53 response. This diagram illustrates 3 such negative feedback loops. Medline=15838523 4.0 s15 PROTEIN p5 s15 PROTEIN p1 s16 PROTEIN p6 s16 PROTEIN p1 s21 PROTEIN p4 s21 PROTEIN p1 inactive inactive inactive active inactive inactive active active active inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active active active active active active inactive inactive inactive inactive Long Name: P53 responsive genes Synonym: Synonym not specified Accession: G04681 inside GENE gn1 Long Name: Mouse double minute 2 Synonym: Synonym not specified Accession: P04536 Pathway Link: P00033|P04496|Insulin/IGF pathway-protein kinase B signaling cascade*P04398|P04663|p53 pathway feedback loops 2*P00059|P01483|p53 pathway inside PROTEIN p4 Long Name: Constitutively photomorphogenic 1 Synonym: Synonym not specified Accession: P04540 inside PROTEIN p5 Long Name: Pirh-2 Synonym: Synonym not specified Accession: P04538 inside PROTEIN p6 Long Name: P73DeltaN Synonym: Synonym not specified Accession: G04685 inside RNA rn1 Long Name: Delta Np73 Synonym: Synonym not specified Accession: P04537 inside PROTEIN p2 Long Name: Tumor protein p73 Synonym: p53-related protein p73 Accession: G04686 inside GENE gn2 Long Name: Mdm2 Synonym: Synonym not specified Accession: G04682 inside GENE gn3 Long Name: Cop-1 Synonym: Synonym not specified Accession: G04683 inside GENE gn4 Long Name: Pirh-2 Synonym: Synonym not specified Accession: G04684 inside GENE gn5 Long Name: P53 Synonym: Synonym not specified Accession: P04539 Pathway Link: P00006|P00273|Apoptosis signaling pathway*P00033|P04497|Insulin/IGF pathway-protein kinase B signaling cascade*P04398|P04668|p53 pathway feedback loops 2*P00059|P01485|p53 pathway inside PROTEIN p1 Long Name: Long name not specified Synonym: Synonym not specified Accession: U05449 Heterodimer Member Info: P53#PROTEIN#P53#P04539;Cop-1#PROTEIN#Constitutively photomorphogenic 1#P04540 inside COMPLEX Complex_br_(Cop_minus_1/P53) Long Name: Long name not specified Synonym: Synonym not specified Accession: U05448 Heterodimer Member Info: Pirh-1#PROTEIN#PMID: 11753569,15547185#P04538#Pirh2 is a RING-H2 domain-containing protein with intrinsic ubiquitin-protein ligase activity. Pirh2 transcription is induced by p53|and its protein physically interacts with p53 and promotes ubiquitination and degradation of p53 independently of Mdm2.;P53#PROTEIN#P53#P04539 inside COMPLEX Complex_br_(Pirh_minus_1/P53) Long Name: P53 Synonym: Synonym not specified Accession: P04539 Pathway Link: P00006|P00273|Apoptosis signaling pathway*P00033|P04497|Insulin/IGF pathway-protein kinase B signaling cascade*P04398|P04668|p53 pathway feedback loops 2*P00059|P01485|p53 pathway inside PROTEIN p1 Long Name: a27_degraded Synonym: Synonym not specified Accession: U05452 inside DEGRADED a27_degraded Long Name: a28_degraded Synonym: Synonym not specified Accession: U05450 inside DEGRADED a28_degraded Long Name: a29_degraded Synonym: Synonym not specified Accession: U05451 inside DEGRADED a29_degraded Long Name: Long name not specified Synonym: Synonym not specified Accession: U05447 Heterodimer Member Info: Mdm2#PROTEIN#Mouse double minute 2#P04536;P53#PROTEIN#P53#P04539 inside COMPLEX Complex_br_(Mdm2/P53) Long Name: Ub Synonym: Synonym not specified Accession: S04838 inside SIMPLE_MOLECULE Ub inside RNA rn2 inside RNA rn3 inside RNA rn4 inside RNA rn5 HETERODIMER_ASSOCIATION 0.33333333333333326,-2.220446049250313E-16 0.6666666666666667,-2.220446049250313E-16 0.43960115308017,0.3583381921598541 0.5703005515194399,-0.03463247493016297 -0.2635195481084933,0.9338830685767663 a1 a7 a25 HETERODIMER_ASSOCIATION 0.6484575927194012,-0.0036736090285447442 -1.1457361530766876,1.499596157133082 a1 a8 a26 DISSOCIATION 0.5600612193091221,0.12240120232881324 0.016646145948411295,0.5643781895066082 a25 a41 a31 a28 DISSOCIATION 0.6387679685108392,0.00684052146707792 0.60138812992572,-0.030282892880848067 0.5016954347920031,0.02536389485906554 -0.005829027184912405,0.625770818856271 a26 a40 a32 a29 STATE_TRANSITION a27 a33 STATE_TRANSITION 0.3333333333333357,0.0 0.666666666666667,8.881784197001252E-16 a28 a34 STATE_TRANSITION 0.6463128414492267,0.020669388399122468 a29 a35 HETERODIMER_ASSOCIATION 0.5040339192315382,-0.011327949649207358 0.3415314878705235,0.0582464024590581 0.6707657439352613,0.02912320122952905 0.32954632094183833,0.7186277826658514 a6 a1 a38 DISSOCIATION -5.788785514491135E-4,0.5996279117743977 a38 a39 a30 a27 TRANSCRIPTION a3 a9 a1 TRANSLATION a9 a2 TRANSCRIPTION a10 sa30 a1 TRANSLATION sa30 a6 TRANSCRIPTION a11 sa31 a1 TRANSLATION sa31 a7 TRANSCRIPTION a12 sa32 a1 TRANSLATION sa32 a8 TRANSCRIPTION a5 sa33 a1 a2