Pathway Human Homo sapiens

TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain

R-HSA-6804115 in Reactome release 97: under TP53 Regulates Transcription of Cell Cycle Genes, with 21 genes placed in it by the mapping files and 0 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-6804115 (mouse), R-RNO-6804115 (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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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

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-6804115.2
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-03-23
Events inside: 14, counted from the record

BTG2 is induced by TP53, leading to cessation of cellular proliferation (Rouault et al. 1996, Duriez et al. 2002). BTG2 binds to the CCR4-NOT complex and promotes mRNA deadenylation activity of this complex. Interaction between BTG2 and CCR4-NOT is needed for the antiproliferative activity of BTG2, but the underlying mechanism has not been elucidated (Rouault et al. 1998, Mauxion et al. 2008, Horiuchi et al. 2009, Doidge et al. 2012, Ezzeddine et al. 2012). Two polo-like kinases, PLK2 and PLK3, are direct transcriptional targets of TP53. TP53-mediated induction of PLK2 may be important for prevention of mitotic catastrophe after spindle damage (Burns et al. 2003). PLK2 is involved in the regulation of centrosome duplication through phosphorylation of centrosome-related proteins CENPJ (Chang et al. 2010) and NPM1 (Krause and Hoffmann 2010). PLK2 is frequently transcriptionally silenced through promoter methylation in B-cell malignancies (Syed et al. 2006). Induction of PLK3 transcription by TP53 (Jen and Cheung 2005) may be important for coordination of M phase events through PLK3-mediated nuclear accumulation of CDC25C (Bahassi et al. 2004). RGCC is induced by TP53 and implicated in cell cycle regulation, possibly through its association with PLK1 (Saigusa et al. 2007). PLAGL1 (ZAC1) is a zinc finger protein directly transcriptionally induced by TP53 (Rozenfeld-Granot et al. 2002). PLAGL1 expression is frequently lost in cancer (Varrault et al. 1998) and PLAGL1 has been implicated in both cell cycle arrest and apoptosis (Spengler et al. 1997), but its mechanism of action remains unknown.

Literature Reactome attaches

Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathwayNat. Genet., 1996, vol. 14, p. 482-6PubMed 8944033
Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the murine homolog of a component of the yeast CCR4 transcriptional regulatory complexJ. Biol. Chem., 1998, vol. 273, p. 22563-9PubMed 9712883
The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor geneGene, 2002, vol. 282, p. 207-14PubMed 11814693
The BTG2 protein is a general activator of mRNA deadenylationEMBO J., 2008, vol. 27, p. 1039-48PubMed 18337750
Structural basis for the antiproliferative activity of the Tob-hCaf1 complexJ. Biol. Chem., 2009, vol. 284, p. 13244-55PubMed 19276069
The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complexPLoS ONE, 2012, vol. 7, p. e51331PubMed 23236473
Evidence providing new insights into TOB-promoted deadenylation and supporting a link between TOB's deadenylation-enhancing and antiproliferative activitiesMol. Cell. Biol., 2012, vol. 32, p. 1089-98PubMed 22252318
Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cellsMol. Cell. Biol., 2003, vol. 23, p. 5556-71PubMed 12897130
PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycleEMBO J., 2010, vol. 29, p. 2395-406PubMed 20531387
Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplicationPLoS ONE, 2010, vol. 5, p. e9849PubMed 20352051
Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignanciesBlood, 2006, vol. 107, p. 250-6PubMed 16160013
Identification of novel p53 target genes in ionizing radiation responseCancer Res., 2005, vol. 65, p. 7666-73PubMed 16140933
Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocationOncogene, 2004, vol. 23, p. 2658-63PubMed 14968113
RGC32, a novel p53-inducible gene, is located on centrosomes during mitosis and results in G2/M arrestOncogene, 2007, vol. 26, p. 1110-21PubMed 17146433
A positive feedback mechanism in the transcriptional activation of Apaf-1 by p53 and the coactivator Zac-1Oncogene, 2002, vol. 21, p. 1469-76PubMed 11896574
hZAC encodes a zinc finger protein with antiproliferative properties and maps to a chromosomal region frequently lost in cancerProc. Natl. Acad. Sci. U.S.A., 1998, vol. 95, p. 8835-40PubMed 9671765
Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brainEMBO J., 1997, vol. 16, p. 2814-25PubMed 9184226

Reactome's record lists 11 orthologous events, R-MMU-6804115 (Mus musculus), R-RNO-6804115 (Rattus norvegicus) among the species this site serves, and 9 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-29 ET · Reactome pathway browser"TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-6804115 with StableID: R-HSA-6804115.2 (accessed 2026-09-29 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 21 genes in this human pathway; showing 1 to 21, 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
GeneBTG2	AuthorityHGNC:1131	Mapping file id7832 NCBI file	EvidenceTAS
GeneCDC25C	AuthorityHGNC:1727	Mapping file id995 NCBI file	EvidenceTAS
GeneCNOT1	AuthorityHGNC:7877	Mapping file id23019 NCBI file	EvidenceTAS
GeneCNOT10	AuthorityHGNC:23817	Mapping file id25904 NCBI file	EvidenceTAS
GeneCNOT11	AuthorityHGNC:25217	Mapping file id55571 NCBI file	EvidenceTAS
GeneCNOT12	AuthorityHGNC:19081	Mapping file id85456 NCBI file	EvidenceTAS
GeneCNOT2	AuthorityHGNC:7878	Mapping file id4848 NCBI file	EvidenceTAS
GeneCNOT3	AuthorityHGNC:7879	Mapping file id4849 NCBI file	EvidenceTAS
GeneCNOT4	AuthorityHGNC:7880	Mapping file id4850 NCBI file	EvidenceTAS
GeneCNOT6	AuthorityHGNC:14099	Mapping file id57472 NCBI file	EvidenceTAS
GeneCNOT6L	AuthorityHGNC:18042	Mapping file id246175 NCBI file	EvidenceTAS
GeneCNOT7	AuthorityHGNC:14101	Mapping file id29883 NCBI file	EvidenceTAS
GeneCNOT8	AuthorityHGNC:9207	Mapping file id9337 NCBI file	EvidenceTAS
GeneCNOT9	AuthorityHGNC:10445	Mapping file id9125 NCBI file	EvidenceTAS
GeneCPAP	AuthorityHGNC:17272	Mapping file id55835 NCBI file	EvidenceTAS
GeneNPM1	AuthorityHGNC:7910	Mapping file id4869 NCBI file	EvidenceTAS
GenePLAGL1	AuthorityHGNC:9046	Mapping file id5325 NCBI file	EvidenceTAS
GenePLK2	AuthorityHGNC:19699	Mapping file id10769 NCBI file	EvidenceTAS
GenePLK3	AuthorityHGNC:2154	Mapping file id1263 NCBI file	EvidenceTAS
GeneRGCC	AuthorityHGNC:20369	Mapping file id28984 NCBI file	EvidenceTAS
GeneTP53	AuthorityHGNC:11998	Mapping file id7157 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

TP53 Regulates Transcription of Cell Cycle GenesR-HSA-679131249 genes

Children

None: no pathway of this release's list names this one as a parent.

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.