p53 Pathway

Background

p53 is a transcription factor and tumor suppressor activated by cellular stresses like DNA damage, oxidative stress, and nutrient deprivation. p53 is activated through both phosphorylation and acetylation, which disrupt its interaction with negative regulators, increase its stability and DNA binding activity, and allow it to bind transcriptional co-activators and modulate transcription. The list of p53 transcriptional targets is ever-expanding; the best-characterized effects of p53 are in promoting cell cycle arrest, apoptosis, or senescence in damaged cells. The p53 name arose from its observed molecular weight (53 kDa) when run on an SDS-PAGE gel.

Cancer Impact

p53 is the most frequently mutated gene (>50%) in human cancer; most of these mutations are missense mutations in the DNA-binding domain, often at one of six hotspot residues. These mutations can be inherited or arise through exposure to mutagens like radiation or viruses (e.g., HPV, the human papillomavirus). These mutations interfere with p53’s ability to activate transcription, and they also have a dominant negative effect on functional p53 through oligomerization. In particular, the loss of p53’s pro-apoptotic effects is especially important to tumorigenesis. Inheriting only one functional copy of the p53 gene causes a large reduction in tumor suppression activity, leading to the development of tumors in early adulthood, a disorder known as Li-Fraumeni syndrome. Recently some impacts of p53 mutations have been characterized as gain-of-function, expanding the mechanisms by which mutant p53 is known to function in cancer.

p53 Pathway Plasmids

Click on a name to find available plasmids for the gene, or browse the gene list below. For multiple isoforms or subunits, individual links to each gene page are provided below. Color is used for clarity and does not indicate a specific relationship.

p53 Pathway

Color is used for clarity and does not indicate a specific relationship.

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p53 Pathway - Gene List

Click on a name to find available plasmids for the gene. For components with multiple isoforms or subunits, individual links to each gene page are provided below.

Symbol	Name
14-3-3-σ	Stratifin
Apaf-1	Apoptotic peptidase activating factor 1
ATM	ATM serine/threonine kinase
ATR	ATR serine/threonine kinase
B99	G-2 and S-phase expressed 1; also known as GTSE1
BAI-1	Brain-specific angiogenesis inhibitor 1
Bax	BCL2-associated X protein
Bid	BH3 interacting domain death agonist
CASP3	Caspase 3, apoptosis-related cysteine peptidase
CASP8	Caspase 8, apoptosis-related cysteine peptidase
CASP9	Caspase 9, apoptosis-related cysteine peptidase
Cyclin B CCNB1 CCNB2 CCNB3	Cyclin B1, 2, or 3
Cyclin D CCND1 CCND2 CCND3	Cyclin D1, 2, or 3
Cyclin E CCNE1 CCNE2	Cyclin E1 or E2
Cyclin G CCNG1 CCNG2	Cyclin G1 or G2
CDC25	Cell division cycle 25C
Cdk4/6 CDK4 CDK6	Cyclin-dependent kinase 4 or 6
CHK1	Checkpoint kinase 1
CHK2	Checkpoint kinase 2
Cop-1	Ring finger and WD repeat domain 2 (RFWD2); E3 ubiquitin protein ligase
cytoC	Cytochrome c
DR5	Tumor necrosis factor receptor superfamily, member 10b
E2F-1	E2F transcription factor 1
Fas	Fas cell surface death receptor
Gadd45 GADD45A GADD45B GADD45G	Growth arrest and DNA-damage-inducible; alpha, beta, or gamma
IGF-BP3	Insulin-like growth factor binding protein 3
KAI	CD82 molecule
Maspin	Serpin family B member 5
MDM2	MDM2 proto-oncogene, E3 ubiquitin protein ligase
MDMX	p53 regulator; also known as MDM4
Noxa	Phorbol-12-myristate-13-acetate-induced protein 1; also known as PMAIP1
p14ARF	Cyclin-dependent kinase inhibitor 2A
p21	Cyclin-dependent kinase inhibitor 1A
p48	Damage-specific DNA binding protein 2, 48kDa
p53	Tumor protein p53
p53AIP1	Tumor protein p53 regulated apoptosis inducing protein 1
p53R2	p53 inducible, ribonucleotide reductase M2 B (RRM2B)
PAG608	Zinc finger, matrin-type 3
PAI	Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
PERP	TP53 apoptosis effector
PIDD	p53-induced death domain protein 1
PIGs	Etoposide induced 2.4
PIRH-2	Ring finger and CHY zinc finger domain containing 1 (RCHY1); E3 ubiquitin protein ligase
PTEN	Phosphatase and tensin homolog
PUMA	BCL2 binding component 3
Reprimo	TP53 dependent G2 arrest mediator candidate
Scotin	Shisa family member 5
Sestrins SESN1 SESN2 SESN3	Sestrins 1, 2, or 3
Siah	Siah E3 ubiquitin protein ligase 1
TSC2	Tuberous sclerosis 2
TSP1	Thrombospondin 1

References

Unravelling mechanisms of p53-mediated tumour suppression. Bieging KT, Mello SS, Attardi LD. Nat Rev Cancer. 2014 May;14(5):359-70. PubMed PMID: 24739573.

Uncovering the role of p53 splice variants in human malignancy: a clinical perspective. Surget S, Khoury MP, Bourdon JC. Onco Targets Ther. 2013 Dec 19;7:57-68. doi: 10.2147/OTT.S53876. PubMed PMID: 24379683.

When mutants gain new powers: news from the mutant p53 field. Brosh R, Rotter V. Nat Rev Cancer. 2009 Oct;9(10):701-13. PubMed PMID: 19693097 .

The expanding universe of p53 targets. Menendez D, Inga A, Resnick MA. Nat Rev Cancer. 2009 Oct;9(10):724-37. PubMed PMID: 19776742.

Germline TP53 mutations and Li-Fraumeni syndrome. Varley JM. Hum Mutat. 2003 Mar;21(3):313-20. PubMed PMID: 12619118.

p53 mutant mice that display early ageing-associated phenotypes. Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A, Donehower LA. Nature. 2002 Jan 3;415(6867):45-53. PubMed PMID: 11780111.

p53 mutations in human cancers. Hollstein M, Sidransky D, Vogelstein B, Harris CC. Science. 1991 Jul 5;253(5015):49-53. PubMed PMID: 1905840.

Recruitment of p300/CBP in p53-dependent signal pathways. Avantaggiati ML, Ogryzko V, Gardner K, Giordano A, Levine AS, Kelly K. Nature. 1997 Jun 27;89(7):1175-84. PubMed PMID: 9215639.

Mutant p53 gain-of-function in cancer. Oren, M. and V. Rotter. Cold Spring Harbor Perspectives in Biology. 2010 Feb;2(2):a001107. PMC PMID: 20182618.