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CDKN1A (cyclin-dependent kinase inhibitor 1A)

Identity

Other namesp21
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)
HGNC (Hugo) CDKN1A
Location 6p21.2
Location_base_pair Starts at 36646459 and ends at 36655108 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  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
    HGNC (Hugo)CDKN1A   1784
    Entrez_Gene (NCBI)CDKN1A  1026  cyclin-dependent kinase inhibitor 1A (p21, Cip1)
    Cards
    AtlasCDKN1AID139
    GeneCards (Weizmann)CDKN1A
    Ensembl (Hinxton)ENSG00000124762 [Gene_View]  CDKN1A [Vega]
    AceView (NCBI)CDKN1A
    Genatlas (Paris)CDKN1A
    euGene (Indiana)1026
    SOURCE (Stanford)NM_000389 NM_078467
    Gene Expression (Array Express) ENSG00000124762
    Genomic and cartography
    GoldenPath (UCSC)CDKN1A  -  6p21.2   chr6:36646459-36655108 +  6p21.2   [Description]    (hg19-Feb_2009)
    EnsemblCDKN1A - 6p21.2 [CytoView]
    Mapping of homologs : NCBICDKN1A [Mapview]
    OMIM116899   
    Gene and transcription
    Gene : Genbank (Entrez)AB209881 AB451290 AB451422 AK298901 AK309512
    Reference sequence (RefSeq transcript) :SRSNM_000389 NM_078467
    Reference transcript : EntrezNM_000389 NM_078467
    RefSeq genomic : SRSAC_000049 AC_000138 NC_000006 NG_009364 NT_007592 NW_001838980 NW_923073
    RefSeq genomic : EntrezAC_000049 AC_000138 NC_000006 NG_009364 NT_007592 NW_001838980 NW_923073
    Consensus coding sequences : CCDS NCBICDKN1A
    Cluster EST : UnigeneHs.370771 [ SRS ] Hs.370771 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)9114
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtP38936 (SRS) P38936 (Expasy) P38936 (Uniprot)
    With graphics : InterProP38936
    Splice isoforms : VarSplice FASTAP38936(VarSplice FASTA)
    Domains : Interpro (SRS)CDI   
    Domains : Interpro (EBI)CDI   
    Related proteins : CluSTrP38936
    Domain families : Pfam SRSCDI (PF02234)   
    Domain families : Pfam SangerCDI (PF02234)   
    Domain families : Pfam NCBIpfam02234   
    Blocks (Seattle)P38936
    Crystal structure of protein : PDB SRS1AXC    2ZVV    2ZVW   
    Crystal structure of protein : PDBSum1AXC    2ZVV    2ZVW   
    Crystal structure of protein : IMB1AXC    2ZVV    2ZVW   
    Crystal structure of protein : PDB RSDB1AXC    2ZVV    2ZVW   
    Human Protein AtlasENSG00000124762
    HPRD00298
    Protein Interaction databases
    DIP (DOE-UCLA)P38936
    IntAct (EBI)P38936
    FunCoupENSG00000124762
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBICDKN1A
    SNP : GeneSNP UtahCDKN1A
    SNP : HGBaseCDKN1A
    Genetic variants : HAPMAPCDKN1A
    Somatic Mutations in Cancer : COSMICCDKN1A 
    Mutations and Diseases : HGMDCDKN1A
    Hereditary diseases : OMIM116899   
    Hereditary diseases : GENETests116899   
    Diseases : Genetic AssociationCDKN1A
    General knowledge
    Homologs : HomoloGeneCDKN1A
    Homology/Alignments : Family Browser UCSCCDKN1A
    Phylogenetic Trees/Animal Genes : TreeFamCDKN1A
    Chemical/Protein Interactions : CTD1026
    Keywords Ontology : AmiGOregulation of cyclin-dependent protein kinase activity  G1/S transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  cyclin-dependent protein kinase holoenzyme complex  protein kinase inhibitor activity  cyclin-dependent protein kinase inhibitor activity  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  response to DNA damage stimulus  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  cell cycle arrest  Ras protein signal transduction  negative regulation of cell proliferation  negative regulation of cell proliferation  induction of apoptosis by intracellular signals  response to UV  response to toxin  senescence  response to organic nitrogen  response to organic cyclic substance  negative regulation of cell growth  cyclin binding  positive regulation of B cell proliferation  organ regeneration  cellular response to extracellular stimulus  protein complex binding  negative regulation of phosphorylation  response to drug  negative regulation of apoptosis  positive regulation of programmed cell death  negative regulation of cyclin-dependent protein kinase activity  positive regulation of anti-apoptosis  response to arsenic  metal ion binding  positive regulation of fibroblast proliferation  response to corticosterone stimulus  response to hyperoxia  
    Keywords Ontology : EGO-EBIregulation of cyclin-dependent protein kinase activity  G1/S transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  cyclin-dependent protein kinase holoenzyme complex  protein kinase inhibitor activity  cyclin-dependent protein kinase inhibitor activity  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  response to DNA damage stimulus  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  cell cycle arrest  Ras protein signal transduction  negative regulation of cell proliferation  negative regulation of cell proliferation  induction of apoptosis by intracellular signals  response to UV  response to toxin  senescence  response to organic nitrogen  response to organic cyclic substance  negative regulation of cell growth  cyclin binding  positive regulation of B cell proliferation  organ regeneration  cellular response to extracellular stimulus  protein complex binding  negative regulation of phosphorylation  response to drug  negative regulation of apoptosis  positive regulation of programmed cell death  negative regulation of cyclin-dependent protein kinase activity  positive regulation of anti-apoptosis  response to arsenic  metal ion binding  positive regulation of fibroblast proliferation  response to corticosterone stimulus  response to hyperoxia  
    Pathways : BIOCARTAInfluence of Ras and Rho proteins on G1 to S Transition [Genes]    Cell Cycle: G1/S Check Point [Genes]    p53 Signaling Pathway [Genes]    Erythropoietin mediated neuroprotection through NF-kB [Genes]    Hypoxia and p53 in the Cardiovascular system [Genes]    ATM Signaling Pathway [Genes]    Effects of calcineurin in Keratinocyte Differentiation [Genes]    Cell Cycle: G2/M Checkpoint [Genes]    Cyclins and Cell Cycle Regulation [Genes]   
    Pathways : KEGGCell cycle
    Other databases
    Probes
    ProbeCancer Cytogenetics (Bari)
    Probes : ImagenesCDKN1A Related clones (RZPD - Berlin)
    Literature
    PubMed499 Pubmed reference(s) in Entrez
    PubGeneCDKN1A

    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 articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    Contributor(s)

    Written04-2001Delphine 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

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    indexed on : Thu Jul 15 14:43:53 CEST 2010
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