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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
LocusID (NCBI) 1026
Location 6p21.2
Location_base_pair Starts at 36646456 and ends at 36655116 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  CDKN1A (6p21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

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.

    Other Leukemias implicated (Data extracted from papers in the Atlas)

    Leukemias 11q23ChildAMLID1615

    Other Solid tumors implicated (Data extracted from papers in the Atlas)

    Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004

    External links

    Nomenclature
    HGNC (Hugo)CDKN1A   1784
    Cards
    AtlasCDKN1AID139
    Entrez_Gene (NCBI)CDKN1A  1026  cyclin-dependent kinase inhibitor 1A (p21, Cip1)
    GeneCards (Weizmann)CDKN1A
    Ensembl (Hinxton)ENSG00000124762 [Gene_View]  chr6:36646456-36655116 [Contig_View]  CDKN1A [Vega]
    ICGC DataPortalENSG00000124762
    cBioPortalCDKN1A
    AceView (NCBI)CDKN1A
    Genatlas (Paris)CDKN1A
    WikiGenes1026
    SOURCE (Princeton)NM_000389 NM_001220777 NM_001220778 NM_001291549 NM_078467
    Genomic and cartography
    GoldenPath (UCSC)CDKN1A  -  6p21.2   chr6:36646456-36655116 +  6p21.1   [Description]    (hg19-Feb_2009)
    EnsemblCDKN1A - 6p21.1 [CytoView]
    Mapping of homologs : NCBICDKN1A [Mapview]
    OMIM116899   
    Gene and transcription
    Genbank (Entrez)AA534613 AB209881 AB451290 AB451422 AI973138
    RefSeq transcript (Entrez)NM_000389 NM_001220777 NM_001220778 NM_001291549 NM_078467
    RefSeq genomic (Entrez)AC_000138 NC_000006 NC_018917 NG_009364 NT_007592 NW_001838980 NW_004929326
    Consensus coding sequences : CCDS (NCBI)CDKN1A
    Cluster EST : UnigeneHs.732576 [ NCBI ]
    CGAP (NCI)Hs.732576
    Alternative Splicing : Fast-db (Paris)GSHG0025686
    Alternative Splicing GalleryENSG00000124762
    Gene ExpressionCDKN1A [ NCBI-GEO ]     CDKN1A [ SEEK ]   CDKN1A [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP38936 (Uniprot)
    NextProtP38936  [Medical]
    With graphics : InterProP38936
    Splice isoforms : SwissVarP38936 (Swissvar)
    Domains : Interpro (EBI)CDI [organisation]  
    Related proteins : CluSTrP38936
    Domain families : Pfam (Sanger)CDI (PF02234)   
    Domain families : Pfam (NCBI)pfam02234   
    DMDM Disease mutations1026
    Blocks (Seattle)P38936
    PDB (SRS)1AXC    2ZVV    2ZVW   
    PDB (PDBSum)1AXC    2ZVV    2ZVW   
    PDB (IMB)1AXC    2ZVV    2ZVW   
    PDB (RSDB)1AXC    2ZVV    2ZVW   
    Human Protein AtlasENSG00000124762 [gene] [tissue] [antibody] [cell] [cancer]
    Peptide AtlasP38936
    HPRD00298
    IPIIPI00009384   IPI00910937   IPI00387000   
    Protein Interaction databases
    DIP (DOE-UCLA)P38936
    IntAct (EBI)P38936
    FunCoupENSG00000124762
    BioGRIDCDKN1A
    InParanoidP38936
    Interologous Interaction database P38936
    IntegromeDBCDKN1A
    STRING (EMBL)CDKN1A
    Ontologies - Pathways
    Ontology : AmiGOregulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  G1/S transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  mitotic cell cycle  cyclin-dependent protein kinase holoenzyme complex  cyclin-dependent protein serine/threonine kinase inhibitor activity  protein binding  nucleus  nucleoplasm  nucleolus  cytosol  protein phosphorylation  cellular response to DNA damage stimulus  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  cell cycle arrest  epidermal growth factor receptor signaling pathway  Ras protein signal transduction  negative regulation of cell proliferation  negative regulation of cell proliferation  fibroblast growth factor receptor signaling pathway  response to UV  response to toxic substance  response to organonitrogen compound  negative regulation of gene expression  cyclin-dependent protein kinase activating kinase activity  negative regulation of cell growth  cyclin binding  positive regulation of B cell proliferation  organ regeneration  cellular response to extracellular stimulus  protein complex binding  regulation of protein import into nucleus, translocation  Fc-epsilon receptor signaling pathway  negative regulation of phosphorylation  response to drug  intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  negative regulation of apoptotic process  positive regulation of programmed cell death  intracellular membrane-bounded organelle  innate immune response  negative regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of protein kinase activity  response to arsenic-containing substance  metal ion binding  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  positive regulation of fibroblast proliferation  response to corticosterone  response to hyperoxia  PCNA-p21 complex  cellular response to ionizing radiation  mitotic cell cycle arrest  cellular senescence  stress-induced premature senescence  intrinsic apoptotic signaling pathway  regulation of DNA biosynthetic process  positive regulation of reactive oxygen species metabolic process  
    Ontology : EGO-EBIregulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  G1/S transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  mitotic cell cycle  cyclin-dependent protein kinase holoenzyme complex  cyclin-dependent protein serine/threonine kinase inhibitor activity  protein binding  nucleus  nucleoplasm  nucleolus  cytosol  protein phosphorylation  cellular response to DNA damage stimulus  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  cell cycle arrest  epidermal growth factor receptor signaling pathway  Ras protein signal transduction  negative regulation of cell proliferation  negative regulation of cell proliferation  fibroblast growth factor receptor signaling pathway  response to UV  response to toxic substance  response to organonitrogen compound  negative regulation of gene expression  cyclin-dependent protein kinase activating kinase activity  negative regulation of cell growth  cyclin binding  positive regulation of B cell proliferation  organ regeneration  cellular response to extracellular stimulus  protein complex binding  regulation of protein import into nucleus, translocation  Fc-epsilon receptor signaling pathway  negative regulation of phosphorylation  response to drug  intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  negative regulation of apoptotic process  positive regulation of programmed cell death  intracellular membrane-bounded organelle  innate immune response  negative regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of protein kinase activity  response to arsenic-containing substance  metal ion binding  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  positive regulation of fibroblast proliferation  response to corticosterone  response to hyperoxia  PCNA-p21 complex  cellular response to ionizing radiation  mitotic cell cycle arrest  cellular senescence  stress-induced premature senescence  intrinsic apoptotic signaling pathway  regulation of DNA biosynthetic process  positive regulation of reactive oxygen species metabolic process  
    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 : KEGGErbB signaling pathway    HIF-1 signaling pathway    FoxO signaling pathway    Cell cycle    p53 signaling pathway    PI3K-Akt signaling pathway    Hepatitis C    Hepatitis B    HTLV-I infection    Epstein-Barr virus infection    Pathways in cancer    Transcriptional misregulation in cancer    Viral carcinogenesis    Proteoglycans in cancer    MicroRNAs in cancer    Glioma    Prostate cancer    Melanoma    Bladder cancer    Chronic myeloid leukemia   
    Protein Interaction DatabaseCDKN1A
    Wikipedia pathwaysCDKN1A
    Gene fusion - rearrangments
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)CDKN1A
    snp3D : Map Gene to Disease1026
    SNP (GeneSNP Utah)CDKN1A
    SNP : HGBaseCDKN1A
    Genetic variants : HAPMAPCDKN1A
    Exome VariantCDKN1A
    1000_GenomesCDKN1A 
    ICGC programENSG00000124762 
    Somatic Mutations in Cancer : COSMICCDKN1A 
    CONAN: Copy Number AnalysisCDKN1A 
    Mutations and Diseases : HGMDCDKN1A
    Mutations and Diseases : intOGenCDKN1A
    Genomic VariantsCDKN1A  CDKN1A [DGVbeta]
    dbVarCDKN1A
    ClinVarCDKN1A
    Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
    Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
    Diseases
    OMIM116899   
    MedgenCDKN1A
    GENETestsCDKN1A
    Disease Genetic AssociationCDKN1A
    Huge Navigator CDKN1A [HugePedia]  CDKN1A [HugeCancerGEM]
    General knowledge
    Homologs : HomoloGeneCDKN1A
    Homology/Alignments : Family Browser (UCSC)CDKN1A
    Phylogenetic Trees/Animal Genes : TreeFamCDKN1A
    Chemical/Protein Interactions : CTD1026
    Chemical/Pharm GKB GenePA104
    Clinical trialCDKN1A
    Cancer Resource (Charite)ENSG00000124762
    Other databases
    Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=CDKN1A
    Probes
    ProbeCancer Cytogenetics (Bari)
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    CoreMineCDKN1A
    iHOPCDKN1A
    OncoSearchCDKN1A

    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 ; Besan̤on, F
    CDKN1A (cyclin-dependent kinase inhibitor 1A)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(3):170-171.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/CDKN1AID139.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Tue Sep 23 18:57:43 CEST 2014

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