CDKN1A (cyclin-dependent kinase inhibitor 1A)

Identity

Other names	p21
	WAF1 (Wild type p53 activated protein-1)
	CIP1 (CDK- interacting protein)
	SDI1 (Senescence cell- derived inhibitor-1)
	CAP20
	MDA-6 (melanoma differentiation-asssociated protein-1)
Hugo	CDKN1A
Location	6p21.2
	CDKN1A (6p21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

DNA/RNA

Description	3 exons (68, 450, 1600 pb ; the first exon is not translated)
Transcription	2,1 kb mRNA, expression regulated at both transcriptional and post-transcriptional levels.

Protein

Description	164 amino acids, 18 kDa. Contains interacting domains with several proteins (see Figure) and a nuclear localization signal.
Expression	in all adult human tissues. CDKN1A expression in the developing mouse embryo is correlated with cell-cycle arrest that precedes terminal differentiation in a variety of tissues.
Localisation	nuclear and cytoplasmic. located predominantly in the nucleus. relocalization to the cytoplasm during the differentiation of immature monocytes.
Function	can interact with cytoplasmic proteins ( pro-caspase-3, ASK-1, JNK, CaM, cyclinD-CDK4). CDKN1A is implicated in regulation of cell growth and cell response to DNA damage. It inhibits cell cycle progression in G1 by binding to G1 cyclin-CDK complexes and to PCNA antigen and may also induce G2 arrest. In response to DNA damage p53 induces CDKN1A expression, which is responsible for the cell cycle arrest at the G1 checkpoint. CDKN1A plays also a role in the protection of cells against apoptosis and its expression is essential to maintain cell survival during differentiation of several cell lineages.
Homology	with p27kip1 and p57kip2 in the N- terminal.

Mutations

Somatic

Analysis of normal and tumor cells revealed two common variants in the CDKN1A gene which were not unique to tumors: a C to A substitution at codon 31 (Ser 31-to-Arg) which does not result in loss of activity and a C to T change in the 3' untranslated region of the CDKN1A gene, 20 bp following the stop codon. In prostate cancer, a single base insertion at codon 35, resulting in frameshift, protein troncation and impairement of activity, has been identified. A Phe to Leu change at codon 63, an Arg to Trp change at position 94 and an Asn to Ser change at position 50 were observed in a Burkitt's lymphoma, a human breast carcinoma and a malignant melanoma cell line, respectively.

External links

	Nomenclature
Hugo	CDKN1A
GDB	CDKN1A
Entrez_Gene	CDKN1A  1026  cyclin-dependent kinase inhibitor 1A (p21, Cip1)
	Cards
Atlas	CDKN1AID139
GeneCards	CDKN1A
Ensembl	CDKN1A [Search_View]   ENSG00000124762 [Gene_View]
Genatlas	CDKN1A
GeneLynx	CDKN1A
eGenome	CDKN1A
euGene	1026
	Genomic and cartography
GoldenPath	CDKN1A  -  6p21.2   chr6:36754465-36763086 +  6p21.2   [Description]    (hg18-Mar_2006)
Ensembl	CDKN1A - 6p21.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	CDKN1A
	Gene and transcription
Genbank	AB209881 [ ENTREZ ]
Genbank	AM392711 [ ENTREZ ]
Genbank	AM392920 [ ENTREZ ]
Genbank	AY008263 [ ENTREZ ]
Genbank	BC000275 [ ENTREZ ]
RefSeq	NM_000389 [ SRS ]    NM_000389 [ ENTREZ ]
RefSeq	NM_078467 [ SRS ]    NM_078467 [ ENTREZ ]
RefSeq	AC_000049 [ SRS ]    AC_000049 [ ENTREZ ]
RefSeq	NC_000006 [ SRS ]    NC_000006 [ ENTREZ ]
RefSeq	NT_007592 [ SRS ]    NT_007592 [ ENTREZ ]
RefSeq	NW_923073 [ SRS ]    NW_923073 [ ENTREZ ]
AceView	CDKN1A AceView - NCBI
Unigene	Hs.370771 [ SRS ]    Hs.370771 [ NCBI ]     HS370771 [ spliceNest ]
Fast-db	9114 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P38936 [ SRS]    P38936 [ EXPASY ]     P38936 [ INTERPRO ]
Interpro	IPR003175 CDI [ SRS ]    IPR003175 CDI [ EBI ]
CluSTr	P38936
Pfam	PF02234 CDI [ SRS ]    PF02234 CDI [ Sanger ]    pfam02234 [ NCBI-CDD ]
Blocks	P38936
PDB	1AXC [ SRS ]    1AXC [ PdbSum ],   1AXC [ IMB ]   1AXC [ RSDB ]
HPRD	00298
	Protein Interaction databases
DIP	P38936
IntAct	P38936
	Polymorphism : SNP, mutations, diseases
OMIM	116899    [ map ]
GENECLINICS	116899
SNP	CDKN1A [dbSNP-NCBI]
SNP	NM_000389 [SNP-NCI]
SNP	NM_078467 [SNP-NCI]
SNP	CDKN1A [GeneSNPs - Utah]  CDKN1A] [HGBASE - SRS]
HAPMAP	CDKN1A [HAPMAP]
COSMIC	CDKN1A [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	CDKN1A
	General knowledge
Family Browser	CDKN1A [UCSC Family Browser]
SOURCE	NM_000389
SOURCE	NM_078467
SMD	Hs.370771
SAGE	Hs.370771
GO	G1/S transition of mitotic cell cycle [Amigo]  G1/S transition of mitotic cell cycle
GO	G2/M transition of mitotic cell cycle [Amigo]  G2/M transition of mitotic cell cycle
GO	cyclin-dependent protein kinase holoenzyme complex [Amigo]  cyclin-dependent protein kinase holoenzyme complex
GO	protein kinase activity [Amigo]  protein kinase activity
GO	cyclin-dependent protein kinase inhibitor activity [Amigo]  cyclin-dependent protein kinase inhibitor activity
GO	cyclin-dependent protein kinase inhibitor activity [Amigo]  cyclin-dependent protein kinase inhibitor activity
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	cytosol [Amigo]  cytosol
GO	response to DNA damage stimulus [Amigo]  response to DNA damage stimulus
GO	cell cycle [Amigo]  cell cycle
GO	cell cycle arrest [Amigo]  cell cycle arrest
GO	zinc ion binding [Amigo]  zinc ion binding
GO	negative regulation of cell proliferation [Amigo]  negative regulation of cell proliferation
GO	induction of apoptosis by intracellular signals [Amigo]  induction of apoptosis by intracellular signals
GO	response to UV [Amigo]  response to UV
GO	kinase activity [Amigo]  kinase activity
GO	negative regulation of cell growth [Amigo]  negative regulation of cell growth
GO	cyclin binding [Amigo]  cyclin binding
GO	positive regulation of B cell proliferation [Amigo]  positive regulation of B cell proliferation
GO	cellular response to extracellular stimulus [Amigo]  cellular response to extracellular stimulus
GO	negative regulation of phosphorylation [Amigo]  negative regulation of phosphorylation
GO	negative regulation of apoptosis [Amigo]  negative regulation of apoptosis
GO	positive regulation of non-apoptotic programmed cell death [Amigo]  positive regulation of non-apoptotic programmed cell death
GO	negative regulation of cyclin-dependent protein kinase activity [Amigo]  negative regulation of cyclin-dependent protein kinase activity
GO	metal ion binding [Amigo]  metal ion binding
GO	positive regulation of fibroblast proliferation [Amigo]  positive regulation of fibroblast proliferation
BIOCARTA	Influence of Ras and Rho proteins on G1 to S Transition    [Genes]
BIOCARTA	ATM Signaling Pathway    [Genes]
BIOCARTA	Effects of calcineurin in Keratinocyte Differentiation    [Genes]
BIOCARTA	Cyclins and Cell Cycle Regulation    [Genes]
BIOCARTA	Erythropoietin mediated neuroprotection through NF-kB    [Genes]
BIOCARTA	Cell Cycle: G1/S Check Point    [Genes]
BIOCARTA	Cell Cycle: G2/M Checkpoint    [Genes]
BIOCARTA	p53 Signaling Pathway    [Genes]
BIOCARTA	Hypoxia and p53 in the Cardiovascular system    [Genes]
KEGG	Cell cycle
PubGene	CDKN1A
TreeFam	CDKN1A
CTD	1026 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	CDKN1A Related clones (RZPD - Berlin)
	PubMed
PubMed	477 Pubmed reference(s) in LocusLink

Bibliography

The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.

Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ

Cell. 1993 ; 75 (4) : 805-816.

PMID 8242751

The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.

Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ

Cell. 1993 ; 75 (4) : 805-816.

PMID 8242751

A single nucleotide substitution at codon 31 (Ser/Arg) defines a polymorphism in a highly conserved region of the p53-inducible gene WAF1/CIP1.

Chedid M, Michieli P, Lengel C, Huppi K, Givol D

Oncogene. 1994 ; 9 (10) : 3021-3024.

PMID 8084608

Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer.

Mousses S, Ozˆßelik H, Lee PD, Malkin D, Bull SB, Andrulis IL

Human molecular genetics. 1995 ; 4 (6) : 1089-1092.

PMID 7655464

p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells.

Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A, Olson EN, Harper JW, Elledge SJ

Science (New York, N.Y.). 1995 ; 267 (5200) : 1024-1027.

PMID 7863329

The growth-regulatory role of p21 (WAF1/CIP1).

Gartel AL, Tyner AL

Progress in molecular and subcellular biology. 1998 ; 20 : 43-71.

PMID 9928526

Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation.

Asada M, Yamada T, Ichijo H, Delia D, Miyazono K, Fukumuro K, Mizutani S

The EMBO journal. 1999 ; 18 (5) : 1223-1234.

PMID 10064589

Transcriptional regulation of the p21((WAF1/CIP1)) gene.

Gartel AL, Tyner AL

Experimental cell research. 1999 ; 246 (2) : 280-289.

PMID 9925742

p21(WAF1/Cip1): more than a break to the cell cycle?

Dotto GP

Biochimica et biophysica acta. 2000 ; 1471 (1) : M43-M56.

PMID 10967424

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	04-2001	Delphine Javelaud and Françoise Besançon
		Institut Curie, Pavillon Pasteur, Unité INSERM 365, 26 rue d'Ulm, 75231 Paris cedex 05, France

Citation

This paper should be referenced as such :

Javelaud D, Besançon F . CDKN1A (cyclin-dependent kinase inhibitor 1A). Atlas Genet Cytogenet Oncol Haematol. April 2001 . URL : http://AtlasGeneticsOncology.org/Genes/CDKN1AID139.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:22:37 2008