GenAge entry for CDKN1A (Homo sapiens)

Gene name (HAGRID: 284)

HGNC symbol
CDKN1A 
Aliases
P21; CIP1; WAF1; SDI1; CAP20; p21CIP1; p21Cip1/Waf1; CDKN1 
Common name
cyclin-dependent kinase inhibitor 1A (p21, Cip1) 

Potential relevance to the human ageing process

Main reason for selection
Entry selected based on evidence directly linking the gene product to ageing in a cellular model system
Description

The tumor suppressor CDKN1A, also known as p21, is a cyclin-dependent kinase inhibitor of CDK2 and CDK4 complexes, and regulates cell cycle progression at G1 via RB1 [2217]. CDKN1A is tightly controlled by p53 (TP53) and its induction predominantly leads to cell cycle arrest, while its repression may have different outcomes depending on context [2218]. Up to now, CDKN1A has been linked to cancer in multiple ways.

Mice lacking p21 undergo normal development, but are defective in G1 checkpoint control [2219]. The deletion of p21 in mice with dysfunctional telomeres prolonged lifespan. The mice exhibited improved hematolymphopoiesis and maintenance of intestinal epithelia without rescuing telomere function. Moreover, they showed rescued proliferation of intestinal progenitor cells and improved repopulation capacity and self-renewal of hematopoietic stem cells [2220]. In mice, using the ear hole closure phenotype, it was shown that regeneration occurs much faster in p21-deficient animals than in controls [2221].

In human cells, an increase in the mRNA level of CDKN1A was observed upon stress-induced premature senescence [2222]. In a study of human longevity polymorphisms two CDKN1A alleles, which are very rare in Italian centenarians, have been identified, leading to the suggestion that they might have potentially detrimental effect to longevity [2223]. Clearly, CDKN1A plays a role in cancer and cell senescence, but its role in human ageing remains unknown.

Cytogenetic information

Cytogenetic band
6p21.2
Location
36,678,679 bp to 36,687,339 bp
Orientation
Plus strand
Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology
Process: GO:0000079; regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0000082; G1/S transition of mitotic cell cycle
GO:0000086; G2/M transition of mitotic cell cycle
GO:0006974; cellular response to DNA damage stimulus
GO:0006977; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0006978; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0007050; cell cycle arrest
GO:0007265; Ras protein signal transduction
GO:0008285; negative regulation of cell proliferation
GO:0009636; response to toxic substance
GO:0010165; response to X-ray
And 35 more GO terms
Cellular component: GO:0000307; cyclin-dependent protein kinase holoenzyme complex
GO:0005634; nucleus
GO:0005654; nucleoplasm
GO:0005730; nucleolus
GO:0005829; cytosol
GO:0043234; protein complex
GO:0048471; perinuclear region of cytoplasm
GO:0070557; PCNA-p21 complex
Function: GO:0004861; cyclin-dependent protein serine/threonine kinase inhibitor activity
GO:0005515; protein binding
GO:0019912; cyclin-dependent protein kinase activating kinase activity
GO:0030332; cyclin binding
GO:0031625; ubiquitin protein ligase binding
GO:0032403; protein complex binding
GO:0046872; metal ion binding
Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge
TP53, TXN, STAT3, AKT1, NGFR, PARP1, CREBBP, NCOR1, HSP90AA1, EP300, PCNA, HSPA8, RB1, FOXO1, APP, A2M, HDAC1, HSPA1A, MAPK8, JUN, CCNA2, MAP3K5, EEF1A1, HSPA9, CDK1, E2F1, HDAC2, MDM2, VCP, UBB, CEBPA, ESR1, TP63, NCOR2, NFE2L2
STRING interaction network
Protein-Protein network diagram for CDKN1A

Retrieve sequences for CDKN1A

Promoter
Promoter
ORF
ORF
CDS
CDS

Homologs in model organisms

Danio rerio
cdkn1a
Mus musculus
Cdkn1a
Rattus norvegicus
Cdkn1a

In other databases

GenAge model organism genes
  • A homolog of this gene for Mus musculus is present as Cdkn1a
LongevityMap
  • This gene is present as CDKN1A
CellAge
  • This gene is present as CDKN1A

Selected references

External links

EPD
HS_CDKN1A
ORF Accession
NM_000389
CDS Accession
NP_000380
OMIM
116899
HPRD
00298
Ensembl
CDKN1A
UniProt/Swiss-Prot
CDN1A_HUMAN
GeneCards
CDKN1A
Entrez Gene
1026
UniGene
370771
GenAtlas
CDKN1A
Internet
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