CDKN1A (cyclin-dependent kinase inhibitor 1A)

2001-04-01   Delphine Javelaud  , Françoise Besançon  

Institut Curie, Pavillon Pasteur, Unité INSERM 365, 26 rue dUlm, 75231 Paris cedex 05, France

Identity

HGNC
LOCATION
6p21.2
IMAGE
Atlas Image
LEGEND
CDKN1A (6p21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
CAP20,CDKN1,CIP1,MDA-6,P21,SDI1,WAF1,p21CIP1
FUSION GENES

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.

Proteins

Atlas Image

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 Burkitts lymphoma, a human breast carcinoma and a malignant melanoma cell line, respectively.

    Implicated in

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    100645891999Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation.Asada M et al
    80846081994A 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 et al
    109674242000p21(WAF1/Cip1): more than a break to the cell cycle?Dotto GP et al
    99257421999Transcriptional regulation of the p21((WAF1/CIP1)) gene.Gartel AL et al
    82427511993The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.Harper JW et al
    76554641995Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer.Mousses S et al
    78633291995p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells.Parker SB et al

    Other Information

    Locus ID:

    NCBI: 1026
    MIM: 116899
    HGNC: 1784
    Ensembl: ENSG00000124762

    Variants:

    dbSNP: 1026
    ClinVar: 1026
    TCGA: ENSG00000124762
    COSMIC: CDKN1A

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000124762ENST00000244741P38936
    ENSG00000124762ENST00000244741A0A024RCX5
    ENSG00000124762ENST00000373711P38936
    ENSG00000124762ENST00000373711A0A024RCX5
    ENSG00000124762ENST00000405375P38936
    ENSG00000124762ENST00000405375A0A024RCX5
    ENSG00000124762ENST00000448526P38936
    ENSG00000124762ENST00000448526A0A024RCX5
    ENSG00000124762ENST00000615513P38936
    ENSG00000124762ENST00000615513A0A024RCX5

    Expression (GTEx)

    0
    50
    100
    150
    200
    250
    300
    350
    400
    450

    Pathways

    PathwaySourceExternal ID
    ErbB signaling pathwayKEGGko04012
    Cell cycleKEGGko04110
    p53 signaling pathwayKEGGko04115
    Jak-STAT signaling pathwayKEGGko04630
    GliomaKEGGko05214
    Prostate cancerKEGGko05215
    MelanomaKEGGko05218
    Bladder cancerKEGGko05219
    Chronic myeloid leukemiaKEGGko05220
    ErbB signaling pathwayKEGGhsa04012
    Cell cycleKEGGhsa04110
    p53 signaling pathwayKEGGhsa04115
    Jak-STAT signaling pathwayKEGGhsa04630
    Pathways in cancerKEGGhsa05200
    GliomaKEGGhsa05214
    Prostate cancerKEGGhsa05215
    MelanomaKEGGhsa05218
    Bladder cancerKEGGhsa05219
    Chronic myeloid leukemiaKEGGhsa05220
    Hepatitis CKEGGko05160
    Hepatitis CKEGGhsa05160
    HTLV-I infectionKEGGko05166
    HTLV-I infectionKEGGhsa05166
    Transcriptional misregulation in cancerKEGGko05202
    Transcriptional misregulation in cancerKEGGhsa05202
    Epstein-Barr virus infectionKEGGhsa05169
    Epstein-Barr virus infectionKEGGko05169
    Viral carcinogenesisKEGGhsa05203
    Viral carcinogenesisKEGGko05203
    PI3K-Akt signaling pathwayKEGGhsa04151
    PI3K-Akt signaling pathwayKEGGko04151
    Hepatitis BKEGGhsa05161
    HIF-1 signaling pathwayKEGGhsa04066
    Proteoglycans in cancerKEGGhsa05205
    Proteoglycans in cancerKEGGko05205
    MicroRNAs in cancerKEGGhsa05206
    MicroRNAs in cancerKEGGko05206
    FoxO signaling pathwayKEGGhsa04068
    Oxytocin signaling pathwayKEGGhsa04921
    Oxytocin signaling pathwayKEGGko04921
    DiseaseREACTOMER-HSA-1643685
    Diseases of signal transductionREACTOMER-HSA-5663202
    PI3K/AKT Signaling in CancerREACTOMER-HSA-2219528
    Constitutive Signaling by AKT1 E17K in CancerREACTOMER-HSA-5674400
    Immune SystemREACTOMER-HSA-168256
    Adaptive Immune SystemREACTOMER-HSA-1280218
    Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
    Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
    PIP3 activates AKT signalingREACTOMER-HSA-1257604
    AKT phosphorylates targets in the cytosolREACTOMER-HSA-198323
    Innate Immune SystemREACTOMER-HSA-168249
    DAP12 interactionsREACTOMER-HSA-2172127
    DAP12 signalingREACTOMER-HSA-2424491
    Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
    Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
    Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
    Signaling by InterleukinsREACTOMER-HSA-449147
    Signal TransductionREACTOMER-HSA-162582
    Signaling by EGFRREACTOMER-HSA-177929
    GAB1 signalosomeREACTOMER-HSA-180292
    Signalling by NGFREACTOMER-HSA-166520
    NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
    PI3K/AKT activationREACTOMER-HSA-198203
    Signaling by PDGFREACTOMER-HSA-186797
    Downstream signal transductionREACTOMER-HSA-186763
    Signaling by SCF-KITREACTOMER-HSA-1433557
    Gene ExpressionREACTOMER-HSA-74160
    Generic Transcription PathwayREACTOMER-HSA-212436
    Transcriptional Regulation by TP53REACTOMER-HSA-3700989
    Cell CycleREACTOMER-HSA-1640170
    Cell Cycle CheckpointsREACTOMER-HSA-69620
    G1/S DNA Damage CheckpointsREACTOMER-HSA-69615
    p53-Dependent G1/S DNA damage checkpointREACTOMER-HSA-69580
    p53-Dependent G1 DNA Damage ResponseREACTOMER-HSA-69563
    Transcriptional activation of p53 responsive genesREACTOMER-HSA-69560
    Transcriptional activation of cell cycle inhibitor p21REACTOMER-HSA-69895
    Cell Cycle, MitoticREACTOMER-HSA-69278
    Mitotic G1-G1/S phasesREACTOMER-HSA-453279
    G1 PhaseREACTOMER-HSA-69236
    Cyclin D associated events in G1REACTOMER-HSA-69231
    G1/S TransitionREACTOMER-HSA-69206
    Cyclin E associated events during G1/S transitionREACTOMER-HSA-69202
    SCF(Skp2)-mediated degradation of p27/p21REACTOMER-HSA-187577
    S PhaseREACTOMER-HSA-69242
    Cyclin A:Cdk2-associated events at S phase entryREACTOMER-HSA-69656
    Synthesis of DNAREACTOMER-HSA-69239
    Switching of origins to a post-replicative stateREACTOMER-HSA-69052
    Orc1 removal from chromatinREACTOMER-HSA-68949
    Regulation of DNA replicationREACTOMER-HSA-69304
    Removal of licensing factors from originsREACTOMER-HSA-69300
    Mitotic G2-G2/M phasesREACTOMER-HSA-453274
    G2/M TransitionREACTOMER-HSA-69275
    DNA ReplicationREACTOMER-HSA-69306
    Cellular responses to stressREACTOMER-HSA-2262752
    Cellular SenescenceREACTOMER-HSA-2559583
    DNA Damage/Telomere Stress Induced SenescenceREACTOMER-HSA-2559586
    Senescence-Associated Secretory Phenotype (SASP)REACTOMER-HSA-2559582
    The role of GTSE1 in G2/M progression after G2 checkpointREACTOMER-HSA-8852276
    TP53 Regulates Transcription of Cell Cycle GenesREACTOMER-HSA-6791312
    TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle ArrestREACTOMER-HSA-6804116
    Platinum drug resistanceKEGGko01524
    Endocrine resistanceKEGGko01522
    Platinum drug resistanceKEGGhsa01524
    Endocrine resistanceKEGGhsa01522
    Transcriptional regulation by the AP-2 (TFAP2) family of transcription factorsREACTOMER-HSA-8864260
    TFAP2 (AP-2) family regulates transcription of cell cycle factorsREACTOMER-HSA-8866911
    Breast cancerKEGGko05224
    Breast cancerKEGGhsa05224
    Interleukin-4 and 13 signalingREACTOMER-HSA-6785807

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    PharmGKB

    Entity IDNameTypeEvidenceAssociationPKPDPMIDs
    PA448871celecoxibChemicalPathwayassociated22336956

    References

    Pubmed IDYearTitleCitations
    376763772024ATM-Mediated translocation of RanBPM regulates DNA damage response by stabilizing p21 in non-small cell lung cancer cells.1
    377344202024p21 Prevents the Exhaustion of CD4(+) T Cells Within the Antitumor Immune Response Against Colorectal Cancer.0
    381081192024Deoxyribonuclease 1-like 3 inhibits colorectal malignancy through antagonizing NEDD4-triggered CDKN1A ubiquitination.0
    381825712024CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression.0
    384477982024Transcriptome analysis of polyploid giant cancer cells and their progeny reveals a functional role for p21 in polyploidization and depolyploidization.2
    376763772024ATM-Mediated translocation of RanBPM regulates DNA damage response by stabilizing p21 in non-small cell lung cancer cells.1
    377344202024p21 Prevents the Exhaustion of CD4(+) T Cells Within the Antitumor Immune Response Against Colorectal Cancer.0
    381081192024Deoxyribonuclease 1-like 3 inhibits colorectal malignancy through antagonizing NEDD4-triggered CDKN1A ubiquitination.0
    381825712024CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression.0
    384477982024Transcriptome analysis of polyploid giant cancer cells and their progeny reveals a functional role for p21 in polyploidization and depolyploidization.2
    360178582023Knockdown of PRKD2 Enhances Chemotherapy Sensitivity in Cervical Cancer via the TP53/CDKN1A Pathway.0
    364181882023Epstein-Barr virus miR-BART2-5p and miR-BART11-5p regulate cell proliferation, apoptosis, and migration by targeting RB and p21 in gastric carcinoma.3
    368768352023The Interplay between Noncoding RNAs and p21 Signaling in Gastrointestinal Cancer: From Tumorigenesis to Metastasis.5
    369321962023MORC4 plays a tumor-promoting role in colorectal cancer via regulating PCGF1/CDKN1A axis in vitro and in vivo.1
    370123882023N6-methyladenosine reader YTHDF2 promotes multiple myeloma cell proliferation through EGR1/p21(cip1/waf1)/CDK2-Cyclin E1 axis-mediated cell cycle transition.5

    Citation

    Delphine Javelaud ; Françoise Besançon

    CDKN1A (cyclin-dependent kinase inhibitor 1A)

    Atlas Genet Cytogenet Oncol Haematol. 2001-04-01

    Online version: http://atlasgeneticsoncology.org/gene/139/cdkn1a-(cyclin-dependent-kinase-inhibitor-1a)