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CDKN1B (cyclin-dependent kinase inhibitor 1 B)

Written1998-05Chrystele Bilhou-Nabera
Cytogénétique,Laboratoire d'Hématologie-Pr RAPHAEL, Pav BROCA - 4eme étage, 78 rue du Général Leclerc, 94275 LE KREMLIN-BICETRE, France

(Note : for Links provided by Atlas : click)

Identity

Other namesKIP1
P27KIP1
HGNC (Hugo) CDKN1B
LocusID (NCBI) 1027
Atlas_Id 116
Location 12p13.1
Location_base_pair Starts at 12870204 and ends at 12875316 bp from pter ( according to hg19-Feb_2009)  [Mapping CDKN1B.png]
Local_order centromere - CDNK1B - ETV6 - PRB - KCNA5 - CACNL1A1 - telomere
 
  CDK1B (12p3) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2016)
APOLD1 (12p13.1) / CDKN1B (12p13.1)CDKN1B (12p13.1) / ADGRG1 (16q21)CDKN1B (12p13.1) / CDKN1B (12p13.1)
ETV6 (12p13.2) / CDKN1B (12p13.1)FN1 (2q35) / CDKN1B (12p13.1)VDAC3 (8p11.21) / CDKN1B (12p13.1)

DNA/RNA

Description coding region from two exons
Transcription 2.5 Kb mRNA; CDKN1B gene regulation by extracellular antiproliferative signals occurs at a post-transcriptional level

Protein

Description 198 amino-acids; 22 kDa; homology to WAF1, limited to a 60 amino acid segment in the N-term half of the protein (residues 28-88); putative bipartite nuclear localization signal near the C-term (153-169); C-term extension of 23 amino acids that contains a consensus Cdc2 phosphorylation site.
Expression expressed in all tissues tested; high levels in skeletal muscle, low levels in liver and kidney.
Localisation nuclear.
Function - CDKN1B is a negative regulator implicated in G1 arrest mediated by TGFb, cell-cell contact, agents that elevate cyclic AMP and rapamycin; CDKN1B binds to and acts as a stoichiometric inhibitor of G1-cyclin-cyclin dependent kinase complexes (cyclin E-Cdk2, cyclin A-Cdk2, cyclin D-Cdk4 (restriction point), controlling G1 to S phase transition or exit from the cell cycle; CDKN1B coordinates the varied inputs from the extracellular environment; post-translational ubiquitin-mediated proteasomal proteolysis represents the major regulatory influence of CDKN1B protein level. - in CDKN1B knockout mouse, CDKN1B defect causes multi-organ hyperplasia with features of gigantism, abnormalities of thymus, retina, pituitary, adrenal glands and gonadal organs (ovulatory defect and female sterility).
Homology Cip1/WAF1

Implicated in

Note
Entity haematological malignancies.
Note hemizygous interstitial deletion is found in 10% of cytogenetically normal AML; monoallelic deletion found in 5% AML cases, but not described in ALL; no case so far of CDKN1B mutations in leukemia samples.
  
Entity primary breast cancers
Prognosis a low nuclear expression of CDKN1B protein is a significant predictor of poor disease-free survival; in contrary, high level of CDKN1B protein expression combined with low level expression of its target (cyclin E-Cdk2) correlates with about 90% 10-yr overall survival in the lymph node-negative subgroup.
  
Entity primary colorectal carcinomas
Prognosis CDKN1B is an independent prognostic marker: low levels are significantly correlated with a poor prognosis.
  

Bibliography

Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.
Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, Massagué J
Cell. 1994 ; 78 (1) : 59-66.
PMID 8033212
 
p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21.
Toyoshima H, Hunter T
Cell. 1994 ; 78 (1) : 67-74.
PMID 8033213
 
Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias.
Pietenpol JA, Bohlander SK, Sato Y, Papadopoulos N, Liu B, Friedman C, Trask BJ, Roberts JM, Kinzler KW, Rowley JD
Cancer research. 1995 ; 55 (6) : 1206-1210.
PMID 7882309
 
Translational control of p27Kip1 accumulation during the cell cycle.
Hengst L, Reed SI
Science (New York, N.Y.). 1996 ; 271 (5257) : 1861-1864.
PMID 8596954
 
Germline configuration of the p27(Kip1) gene in childhood acute lymphoblastic leukemia (ALL).
Seriu T, Erz D, Bartram CR
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 ; 10 (2) : page 345.
PMID 8637245
 
Deletions of CDKN1B and ETV6 in acute myeloid leukemia and myelodysplastic syndromes without cytogenetic evidence of 12p abnormalities.
Andreasson P, Johansson B, Arheden K, Billström R, Mitelman F, Höglund M
Genes, chromosomes & cancer. 1997 ; 19 (2) : 77-83.
PMID 9171997
 
Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.
Catzavelos C, Bhattacharya N, Ung YC, Wilson JA, Roncari L, Sandhu C, Shaw P, Yeger H, Morava-Protzner I, Kapusta L, Franssen E, Pritchard KI, Slingerland JM
Nature medicine. 1997 ; 3 (2) : 227-230.
PMID 9018244
 
Molecular analysis of cyclin-dependent kinase inhibitors in human leukemias.
Hayette S, Thomas X, Bertrand Y, Tigaud I, Callanan M, Thiebaut A, Charrin C, Archimbaud E, Magaud JP, Rimokh R
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1997 ; 11 (10) : 1696-1699.
PMID 9324291
 
Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas.
Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF, Jessup JM, Pagano M
Nature medicine. 1997 ; 3 (2) : 231-234.
PMID 9018245
 
Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients.
Porter PL, Malone KE, Heagerty PJ, Alexander GM, Gatti LA, Firpo EJ, Daling JR, Roberts JM
Nature medicine. 1997 ; 3 (2) : 222-225.
PMID 9018243
 
Cancer prognostics: past, present and p27.
Steeg PS, Abrams JS
Nature medicine. 1997 ; 3 (2) : 152-154.
PMID 9018230
 

Citation

This paper should be referenced as such :
Bilhou-Nabera, C
CDKN1B (cyclin-dependent kinase inhibitor 1 B )
Atlas Genet Cytogenet Oncol Haematol. 1998;2(4):115-116.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CDKN1BID116.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 6 ]
  12p abnormalities in myeloid malignancies
Classification of myelodysplastic syndromes 2015
Classification of myelodysplasic syndromes 1999
der(12)t(1;12)(q11-21;p11-13)
t(8;12)(q12;p13)
t(10;12)(q24;p13) ETV6/GOT1

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 7 ]
  Thyroid: Anaplastic (undifferentiated) carcinoma
Esophagus: Barrett's esophagus, dysplasia and adenocarcinoma
Neuro-Endocrine/Endocrine System: Carcinoid tumors
Breast: Ductal carcinoma
Lymphangioleiomyomatosis
Soft Tissues: Lymphangioleiomyoma
Neuro-Endocrine/Endocrine System: Pituitary adenomas
Prostate tumors: an overview

External links

Nomenclature
HGNC (Hugo)CDKN1B   1785
Cards
AtlasCDKN1BID116
Entrez_Gene (NCBI)CDKN1B  1027  cyclin-dependent kinase inhibitor 1B
AliasesCDKN4; KIP1; MEN1B; MEN4; 
P27KIP1
GeneCards (Weizmann)CDKN1B
Ensembl hg19 (Hinxton)ENSG00000111276 [Gene_View]  chr12:12870204-12875316 [Contig_View]  CDKN1B [Vega]
Ensembl hg38 (Hinxton)ENSG00000111276 [Gene_View]  chr12:12870204-12875316 [Contig_View]  CDKN1B [Vega]
ICGC DataPortalENSG00000111276
TCGA cBioPortalCDKN1B
AceView (NCBI)CDKN1B
Genatlas (Paris)CDKN1B
WikiGenes1027
SOURCE (Princeton)CDKN1B
Genomic and cartography
GoldenPath hg19 (UCSC)CDKN1B  -     chr12:12870204-12875316 +  12p13.1-p12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)CDKN1B  -     12p13.1-p12   [Description]    (hg38-Dec_2013)
EnsemblCDKN1B - 12p13.1-p12 [CytoView hg19]  CDKN1B - 12p13.1-p12 [CytoView hg38]
Mapping of homologs : NCBICDKN1B [Mapview hg19]  CDKN1B [Mapview hg38]
OMIM600778   610755   
Gene and transcription
Genbank (Entrez)AA833962 AB451291 AB451423 AF247551 AJ616234
RefSeq transcript (Entrez)NM_004064
RefSeq genomic (Entrez)NC_000012 NC_018923 NG_016341 NT_009714 NW_004929383
Consensus coding sequences : CCDS (NCBI)CDKN1B
Cluster EST : UnigeneHs.238990 [ NCBI ]
CGAP (NCI)Hs.238990
Alternative Splicing GalleryENSG00000111276
Gene ExpressionCDKN1B [ NCBI-GEO ]   CDKN1B [ EBI - ARRAY_EXPRESS ]   CDKN1B [ SEEK ]   CDKN1B [ MEM ]
Gene Expression Viewer (FireBrowse)CDKN1B [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1027
GTEX Portal (Tissue expression)CDKN1B
Protein : pattern, domain, 3D structure
UniProt/SwissProtP46527 (Uniprot)
NextProtP46527  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP46527
Splice isoforms : SwissVarP46527 (Swissvar)
PhosPhoSitePlusP46527
Domains : Interpro (EBI)CDI    CDKN1B   
Domain families : Pfam (Sanger)CDI (PF02234)   
Domain families : Pfam (NCBI)pfam02234   
DMDM Disease mutations1027
Blocks (Seattle)CDKN1B
PDB (SRS)1H27    1JSU    2AST   
PDB (PDBSum)1H27    1JSU    2AST   
PDB (IMB)1H27    1JSU    2AST   
PDB (RSDB)1H27    1JSU    2AST   
Structural Biology KnowledgeBase1H27    1JSU    2AST   
SCOP (Structural Classification of Proteins)1H27    1JSU    2AST   
CATH (Classification of proteins structures)1H27    1JSU    2AST   
SuperfamilyP46527
Human Protein AtlasENSG00000111276
Peptide AtlasP46527
HPRD02867
IPIIPI00006991   IPI01011627   IPI00852705   IPI00853130   
Protein Interaction databases
DIP (DOE-UCLA)P46527
IntAct (EBI)P46527
FunCoupENSG00000111276
BioGRIDCDKN1B
STRING (EMBL)CDKN1B
ZODIACCDKN1B
Ontologies - Pathways
QuickGOP46527
Ontology : AmiGOregulation of cyclin-dependent protein serine/threonine kinase activity  G1/S transition of mitotic cell cycle  G1/S transition of mitotic cell cycle  response to hypoxia  cyclin-dependent protein serine/threonine kinase inhibitor activity  transforming growth factor beta receptor, cytoplasmic mediator activity  protein binding  nucleus  nucleoplasm  cytoplasm  endosome  cytosol  potassium ion transport  activation of cysteine-type endopeptidase activity involved in apoptotic process  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  Notch signaling pathway  sensory perception of sound  positive regulation of cell proliferation  negative regulation of cell proliferation  negative regulation of cell proliferation  cysteine-type endopeptidase activator activity involved in apoptotic process  response to glucose  positive regulation of cell death  protein phosphatase binding  negative regulation of cell growth  Hsp70 protein binding  positive regulation of microtubule polymerization  Cul4A-RING E3 ubiquitin ligase complex  response to estradiol  protein complex binding  negative regulation of kinase activity  negative regulation of phosphorylation  response to drug  negative regulation of apoptotic process  response to amino acid  response to peptide hormone  positive regulation of protein catabolic process  negative regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of cell cycle  negative regulation of transcription, DNA-templated  negative regulation of mitotic cell cycle  response to cadmium ion  autophagic cell death  inner ear development  chaperone binding  negative regulation of cellular component movement  negative regulation of epithelial cell proliferation involved in prostate gland development  cellular response to antibiotic  cellular response to lithium ion  cellular response to organic cyclic compound  mitotic cell cycle arrest  negative regulation of vascular smooth muscle cell proliferation  
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  response to hypoxia  cyclin-dependent protein serine/threonine kinase inhibitor activity  transforming growth factor beta receptor, cytoplasmic mediator activity  protein binding  nucleus  nucleoplasm  cytoplasm  endosome  cytosol  potassium ion transport  activation of cysteine-type endopeptidase activity involved in apoptotic process  DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest  cell cycle arrest  Notch signaling pathway  sensory perception of sound  positive regulation of cell proliferation  negative regulation of cell proliferation  negative regulation of cell proliferation  cysteine-type endopeptidase activator activity involved in apoptotic process  response to glucose  positive regulation of cell death  protein phosphatase binding  negative regulation of cell growth  Hsp70 protein binding  positive regulation of microtubule polymerization  Cul4A-RING E3 ubiquitin ligase complex  response to estradiol  protein complex binding  negative regulation of kinase activity  negative regulation of phosphorylation  response to drug  negative regulation of apoptotic process  response to amino acid  response to peptide hormone  positive regulation of protein catabolic process  negative regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of cyclin-dependent protein serine/threonine kinase activity  positive regulation of cell cycle  negative regulation of transcription, DNA-templated  negative regulation of mitotic cell cycle  response to cadmium ion  autophagic cell death  inner ear development  chaperone binding  negative regulation of cellular component movement  negative regulation of epithelial cell proliferation involved in prostate gland development  cellular response to antibiotic  cellular response to lithium ion  cellular response to organic cyclic compound  mitotic cell cycle arrest  negative regulation of vascular smooth muscle cell proliferation  
Pathways : BIOCARTARegulation of p27 Phosphorylation during Cell Cycle Progression [Genes]    Cyclins and Cell Cycle Regulation [Genes]    CTCF: First Multivalent Nuclear Factor [Genes]    Cell Cycle: G1/S Check Point [Genes]    CDK Regulation of DNA Replication [Genes]    PTEN dependent cell cycle arrest and apoptosis [Genes]    Influence of Ras and Rho proteins on G1 to S Transition [Genes]   
Pathways : KEGGErbB signaling pathway    HIF-1 signaling pathway    FoxO signaling pathway    Cell cycle    PI3K-Akt signaling pathway    Hepatitis B    Measles    Epstein-Barr virus infection    Pathways in cancer    Transcriptional misregulation in cancer    Viral carcinogenesis    MicroRNAs in cancer    Prostate cancer    Chronic myeloid leukemia    Small cell lung cancer   
REACTOMEP46527 [protein]
REACTOME PathwaysR-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence [pathway]
REACTOME PathwaysR-HSA-5625900 RHO GTPases activate CIT [pathway]
REACTOME PathwaysR-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer [pathway]
REACTOME PathwaysR-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) [pathway]
REACTOME PathwaysR-HSA-69202 Cyclin E associated events during G1/S transition [pathway]
REACTOME PathwaysR-HSA-68949 Orc1 removal from chromatin [pathway]
REACTOME PathwaysR-HSA-198323 AKT phosphorylates targets in the cytosol [pathway]
REACTOME PathwaysR-HSA-69563 p53-Dependent G1 DNA Damage Response [pathway]
REACTOME PathwaysR-HSA-69231 Cyclin D associated events in G1 [pathway]
REACTOME PathwaysR-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 [pathway]
REACTOME PathwaysR-HSA-68949 Orc1 removal from chromatin [pathway]
REACTOME PathwaysR-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 [pathway]
REACTOME PathwaysR-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkCDKN1B
Wikipedia pathwaysCDKN1B
Orthology - Evolution
OrthoDB1027
GeneTree (enSembl)ENSG00000111276
Phylogenetic Trees/Animal Genes : TreeFamCDKN1B
Homologs : HomoloGeneCDKN1B
Homology/Alignments : Family Browser (UCSC)CDKN1B
Gene fusions - Rearrangements
Fusion : MitelmanAPOLD1/CDKN1B [12p13.1/12p13.1]  [t(12;12)(p13;p13)]  
Fusion: TCGAAPOLD1 12p13.1 CDKN1B 12p13.1 BRCA
Polymorphisms : SNP, variants
NCBI Variation ViewerCDKN1B [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CDKN1B
dbVarCDKN1B
ClinVarCDKN1B
1000_GenomesCDKN1B 
Exome Variant ServerCDKN1B
ExAC (Exome Aggregation Consortium)CDKN1B (select the gene name)
Genetic variants : HAPMAP1027
Genomic Variants (DGV)CDKN1B [DGVbeta]
Mutations
ICGC Data PortalCDKN1B 
TCGA Data PortalCDKN1B 
Broad Tumor PortalCDKN1B
OASIS PortalCDKN1B [ Somatic mutations - Copy number]
Cancer Gene: CensusCDKN1B 
Somatic Mutations in Cancer : COSMICCDKN1B 
intOGen PortalCDKN1B
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Mendelian genes
BioMutasearch CDKN1B
DgiDB (Drug Gene Interaction Database)CDKN1B
DoCM (Curated mutations)CDKN1B (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CDKN1B (select a term)
intoGenCDKN1B
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)12:12870204-12875316  ENSG00000111276
CONAN: Copy Number AnalysisCDKN1B 
Mutations and Diseases : HGMDCDKN1B
OMIM600778    610755   
MedgenCDKN1B
Genetic Testing Registry CDKN1B
NextProtP46527 [Medical]
TSGene1027
GENETestsCDKN1B
Huge Navigator CDKN1B [HugePedia]
snp3D : Map Gene to Disease1027
BioCentury BCIQCDKN1B
ClinGenCDKN1B
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1027
Chemical/Pharm GKB GenePA105
Clinical trialCDKN1B
Miscellaneous
canSAR (ICR)CDKN1B (select the gene name)
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=CDKN1B
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCDKN1B
EVEXCDKN1B
GoPubMedCDKN1B
iHOPCDKN1B
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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