Pathway Human Homo sapiens

TP53 Regulates Transcription of Cell Death Genes

R-HSA-5633008 in Reactome release 97: under Transcriptional Regulation by TP53, with 44 genes placed in it by the mapping files and 4 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-5633008 (mouse), R-RNO-5633008 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-5633008.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-03-23
Last updated: 2016-06-27
Events inside: 4, counted from the record

The tumor suppressor TP53 (p53) exerts its tumor suppressive role in part by regulating transcription of a number of genes involved in cell death, mainly apoptotic cell death. The majority of apoptotic genes that are transcriptional targets of TP53 promote apoptosis, but there are also several TP53 target genes that inhibit apoptosis, providing cells with an opportunity to attempt to repair the damage and/or recover from stress.

Pro-apoptotic transcriptional targets of TP53 involve TRAIL death receptors TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2), as well as the FASL/CD95L death receptor FAS (CD95). TRAIL receptors and FAS induce pro-apoptotic signaling in response to external stimuli via extrinsic apoptosis pathway (Wu et al. 1997, Takimoto et al. 2000, Guan et al. 2001, Liu et al. 2004, Ruiz de Almodovar et al. 2004, Liu et al. 2005, Schilling et al. 2009, Wilson et al. 2013). IGFBP3 is a transcriptional target of TP53 that may serve as a ligand for a novel death receptor TMEM219 (Buckbinder et al. 1995, Ingermann et al. 2010).

TP53 regulates expression of a number of genes involved in the intrinsic apoptosis pathway, triggered by the cellular stress. Some of TP53 targets, such as BAX, BID, PMAIP1 (NOXA), BBC3 (PUMA) and probably BNIP3L, AIFM2, STEAP3, TRIAP1 and TP53AIP1, regulate the permeability of the mitochondrial membrane and/or cytochrome C release (Miyashita and Reed 1995, Oda et al. 2000, Samuels-Lev et al. 2001, Nakano and Vousden 2001, Sax et al. 2002, Passer et al. 2003, Bergamaschi et al. 2004, Li et al. 2004, Fei et al. 2004, Wu et al. 2004, Park and Nakamura 2005, Patel et al. 2008, Wang et al. 2012, Wilson et al. 2013). Other pro-apoptotic genes, either involved in the intrinsic apoptosis pathway, extrinsic apoptosis pathway or pyroptosis (inflammation-related cell death), which are transcriptionally regulated by TP53 are cytosolic caspase activators, such as APAF1, PIDD1, and NLRC4, and caspases themselves, such as CASP1, CASP6 and CASP10 (Lin et al. 2000, Robles et al. 2001, Gupta et al. 2001, MacLachlan and El-Deiry 2002, Rikhof et al. 2003, Sadasivam et al. 2005, Brough and Rothwell 2007).

It is uncertain how exactly some of the pro-apoptotic TP53 targets, such as TP53I3 (PIG3), RABGGTA, BCL2L14, BCL6, NDRG1 and PERP contribute to apoptosis (Attardi et al. 2000, Guo et al. 2001, Samuels-Lev et al. 2001, Contente et al. 2002, Ihrie et al. 2003, Bergamaschi et al. 2004, Stein et al. 2004, Phan and Dalla-Favera 2004, Jen and Cheung 2005, Margalit et al. 2006, Zhang et al. 2007, Saito et al. 2009, Davies et al. 2009, Giam et al. 2012).

TP53 is stabilized in response to cellular stress by phosphorylation on at least serine residues S15 and S20. Since TP53 stabilization precedes the activation of cell death genes, the TP53 tetramer phosphorylated at S15 and S20 is shown as a regulator of pro-apoptotic/pro-cell death genes. Some pro-apoptotic TP53 target genes, such as TP53AIP1, require additional phosphorylation of TP53 at serine residue S46 (Oda et al. 2000, Taira et al. 2007). Phosphorylation of TP53 at S46 is regulated by another TP53 pro-apoptotic target, TP53INP1 (Okamura et al. 2001, Tomasini et al. 2003). Additional post-translational modifications of TP53 may be involved in transcriptional regulation of genes presented in this pathway and this information will be included as evidence becomes available.

Activation of some pro-apoptotic TP53 targets, such as BAX, FAS, BBC3 (PUMA) and TP53I3 (PIG3) requires the presence of the complex of TP53 and an ASPP protein, either PPP1R13B (ASPP1) or TP53BP2 (ASPP2) (Samuels-Lev et al. 2001, Bergamaschi et al. 2004, Patel et al. 2008, Wilson et al. 2013), indicating how the interaction with specific co-factors modulates the cellular response/outcome.

TP53 family members TP63 and or TP73 can also activate some of the pro-apoptotic TP53 targets, such as FAS, BAX, BBC3 (PUMA), TP53I3 (PIG3), CASP1 and PERP (Bergamaschi et al. 2004, Jain et al. 2005, Ihrie et al. 2005, Patel et al. 2008, Schilling et al. 2009, Celardo et al. 2013).

For a review of the role of TP53 in apoptosis and pro-apoptotic transcriptional targets of TP53, please refer to Riley et al. 2008, Murray-Zmijewski et al. 2008, Bieging et al. 2014, Kruiswijk et al. 2015.

Literature Reactome attaches

KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor geneNat. Genet., 1997, vol. 17, p. 141-3PubMed 9326928
Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding siteOncogene, 2000, vol. 19, p. 1735-43PubMed 10777207
Evidence that the death receptor DR4 is a DNA damage-inducible, p53-regulated geneJ. Cell. Physiol., 2001, vol. 188, p. 98-105PubMed 11382926
p53 upregulates death receptor 4 expression through an intronic p53 binding siteCancer Res., 2004, vol. 64, p. 5078-83PubMed 15289308
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) decoy receptor TRAIL-R3 is up-regulated by p53 in breast tumor cells through a mechanism involving an intronic p53-binding siteJ. Biol. Chem., 2004, vol. 279, p. 4093-101PubMed 14623878
Decoy receptor 2 (DcR2) is a p53 target gene and regulates chemosensitivityCancer Res., 2005, vol. 65, p. 9169-75PubMed 16230375
Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 family

Reactome's record lists 14 orthologous events, R-RNO-5633008 (Rattus norvegicus), R-MMU-5633008 (Mus musculus) among the species this site serves, and 12 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"TP53 Regulates Transcription of Cell Death Genes". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-5633008 with StableID: R-HSA-5633008.4 (accessed 2026-10-01 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 44 genes in this human pathway; showing 1 to 44, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneAIFM2	AuthorityHGNC:21411	Mapping file id84883 NCBI file	EvidenceTAS
GeneAPAF1	AuthorityHGNC:576	Mapping file id317 NCBI file	EvidenceTAS
GeneATM	AuthorityHGNC:795	Mapping file id472 NCBI file	EvidenceTAS
GeneBAX	AuthorityHGNC:959	Mapping file id581 NCBI file	EvidenceTAS
GeneBBC3	AuthorityHGNC:17868	Mapping file id27113 NCBI file	EvidenceTAS
GeneBCL2L14	AuthorityHGNC:16657	Mapping file id79370 NCBI file	EvidenceTAS
GeneBCL6	AuthorityHGNC:1001	Mapping file id604 NCBI file	EvidenceTAS
GeneBID	AuthorityHGNC:1050	Mapping file id637 NCBI file	EvidenceTAS
GeneBIRC5	AuthorityHGNC:593	Mapping file id332 NCBI file	EvidenceTAS
GeneBNIP3L	AuthorityHGNC:1085	Mapping file id665 NCBI file	EvidenceTAS
GeneCASP1	AuthorityHGNC:1499	Mapping file id834 NCBI file	EvidenceTAS
GeneCASP10	AuthorityHGNC:1500	Mapping file id843 NCBI file	EvidenceTAS
GeneCASP2	AuthorityHGNC:1503	Mapping file id835 NCBI file	EvidenceTAS
GeneCASP6	AuthorityHGNC:1507	Mapping file id839 NCBI file	EvidenceTAS
GeneCHM	AuthorityHGNC:1940	Mapping file id1121 NCBI file	EvidenceTAS
GeneCRADD	AuthorityHGNC:2340	Mapping file id8738 NCBI file	EvidenceTAS
GeneCREBBP	AuthorityHGNC:2348	Mapping file id1387 NCBI file	EvidenceTAS
GeneFAS	AuthorityHGNC:11920	Mapping file id355 NCBI file	EvidenceTAS
GeneIGFBP3	AuthorityHGNC:5472	Mapping file id3486 NCBI file	EvidenceTAS
GeneNDRG1	AuthorityHGNC:7679	Mapping file id10397 NCBI file	EvidenceTAS
GeneNLRC4	AuthorityHGNC:16412	Mapping file id58484 NCBI file	EvidenceTAS
GenePERP	AuthorityHGNC:17637	Mapping file id64065 NCBI file	EvidenceTAS
GenePIDD1	AuthorityHGNC:16491	Mapping file id55367 NCBI file	EvidenceTAS
GenePMAIP1	AuthorityHGNC:9108	Mapping file id5366 NCBI file	EvidenceTAS
GenePPP1R13B	AuthorityHGNC:14950	Mapping file id23368 NCBI file	EvidenceTAS
GenePRELID1	AuthorityHGNC:30255	Mapping file id27166 NCBI file	EvidenceTAS
GenePRELID3A	AuthorityHGNC:24639	Mapping file id10650 NCBI file	EvidenceTAS
GeneRABGGTA	AuthorityHGNC:9795	Mapping file id5875 NCBI file	EvidenceTAS
GeneRABGGTB	AuthorityHGNC:9796	Mapping file id5876 NCBI file	EvidenceTAS
GeneSTEAP3	AuthorityHGNC:24592	Mapping file id55240 NCBI file	EvidenceTAS
GeneTMEM219	AuthorityHGNC:25201	Mapping file id124446 NCBI file	EvidenceTAS
GeneTNFRSF10A	AuthorityHGNC:11904	Mapping file id8797 NCBI file	EvidenceTAS
GeneTNFRSF10B	AuthorityHGNC:11905	Mapping file id8795 NCBI file	EvidenceTAS
GeneTNFRSF10C	AuthorityHGNC:11906	Mapping file id8794 NCBI file	EvidenceTAS
GeneTNFRSF10D	AuthorityHGNC:11907	Mapping file id8793 NCBI file	EvidenceTAS
GeneTP53	AuthorityHGNC:11998	Mapping file id7157 NCBI file	EvidenceTAS
GeneTP53AIP1	AuthorityHGNC:29984	Mapping file id63970 NCBI file	EvidenceTAS
GeneTP53BP2	AuthorityHGNC:12000	Mapping file id7159 NCBI file	EvidenceTAS
GeneTP53I3	AuthorityHGNC:19373	Mapping file id9540 NCBI file	EvidenceTAS
GeneTP53INP1	AuthorityHGNC:18022	Mapping file id94241 NCBI file	EvidenceTAS
GeneTP63	AuthorityHGNC:15979	Mapping file id8626 NCBI file	EvidenceTAS
GeneTP73	AuthorityHGNC:12003	Mapping file id7161 NCBI file	EvidenceTAS
GeneTRIAP1	AuthorityHGNC:26937	Mapping file id51499 NCBI file	EvidenceTAS
GeneZNF420	AuthorityHGNC:20649	Mapping file id147923 NCBI file	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Transcriptional Regulation by TP53R-HSA-3700989361 genes

Children

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.