CDKN1B (cyclin-dependent kinase inhibitor 1 B )

Identity

Other names	KIP1
	P27KIP1
Hugo	CDKN1B
Location	12p13
Local_order	centromere - CDNK1B - ETV6 - PRB - KCNA5 - CACNL1A1 - telomere
	CDK1B (12p3) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

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

Entity	haematological malignancies.
Note	hemizygous interstitial deletion is found in 10% of cytogenetically normal ANLL; monoallelic deletion found in 5% ANLL 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.

External links

	Nomenclature
Hugo	CDKN1B
GDB	CDKN1B
Entrez_Gene	CDKN1B  1027  cyclin-dependent kinase inhibitor 1B (p27, Kip1)
	Cards
Atlas	CDKN1BID116
GeneCards	CDKN1B
Ensembl	CDKN1B [Search_View]   ENSG00000111276 [Gene_View]
Genatlas	CDKN1B
GeneLynx	CDKN1B
eGenome	CDKN1B
euGene	1027
	Genomic and cartography
GoldenPath	CDKN1B  -  12p13   chr12:12761576-12766569 +  12p13.1-p12   [Description]    (hg18-Mar_2006)
Ensembl	CDKN1B - 12p13.1-p12 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	CDKN1B
	Gene and transcription
Genbank	AF247551 [ ENTREZ ]
Genbank	AJ616234 [ ENTREZ ]
Genbank	AM392564 [ ENTREZ ]
Genbank	AM393540 [ ENTREZ ]
Genbank	AM393634 [ ENTREZ ]
RefSeq	NM_004064 [ SRS ]    NM_004064 [ ENTREZ ]
RefSeq	AC_000055 [ SRS ]    AC_000055 [ ENTREZ ]
RefSeq	NC_000012 [ SRS ]    NC_000012 [ ENTREZ ]
RefSeq	NT_009714 [ SRS ]    NT_009714 [ ENTREZ ]
RefSeq	NW_925328 [ SRS ]    NW_925328 [ ENTREZ ]
AceView	CDKN1B AceView - NCBI
Unigene	Hs.238990 [ SRS ]    Hs.238990 [ NCBI ]     HS238990 [ spliceNest ]
Fast-db	2878 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P46527 [ SRS]    P46527 [ EXPASY ]     P46527 [ INTERPRO ]
Interpro	IPR003175 CDI [ SRS ]    IPR003175 CDI [ EBI ]
Interpro	IPR015456 Cyclin_inhib_p27 [ SRS ]    IPR015456 Cyclin_inhib_p27 [ EBI ]
CluSTr	P46527
Pfam	PF02234 CDI [ SRS ]    PF02234 CDI [ Sanger ]    pfam02234 [ NCBI-CDD ]
Blocks	P46527
PDB	1H27 [ SRS ]    1H27 [ PdbSum ],   1H27 [ IMB ]   1H27 [ RSDB ]
PDB	1JSU [ SRS ]    1JSU [ PdbSum ],   1JSU [ IMB ]   1JSU [ RSDB ]
PDB	2AST [ SRS ]    2AST [ PdbSum ],   2AST [ IMB ]   2AST [ RSDB ]
HPRD	02867
	Protein Interaction databases
DIP	P46527
IntAct	P46527
	Polymorphism : SNP, mutations, diseases
OMIM	600778;610755    [ map ]
GENECLINICS	600778;610755
SNP	CDKN1B [dbSNP-NCBI]
SNP	NM_004064 [SNP-NCI]
SNP	CDKN1B [GeneSNPs - Utah]  CDKN1B] [HGBASE - SRS]
HAPMAP	CDKN1B [HAPMAP]
COSMIC	CDKN1B [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	CDKN1B
	General knowledge
Family Browser	CDKN1B [UCSC Family Browser]
SOURCE	NM_004064
SMD	Hs.238990
SAGE	Hs.238990
GO	G1/S transition of mitotic cell cycle [Amigo]  G1/S transition of mitotic cell cycle
GO	cyclin-dependent protein kinase inhibitor activity [Amigo]  cyclin-dependent protein kinase inhibitor activity
GO	transforming growth factor beta receptor, cytoplasmic mediator activity [Amigo]  transforming growth factor beta receptor, cytoplasmic mediator activity
GO	protein binding [Amigo]  protein binding
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	cytosol [Amigo]  cytosol
GO	potassium ion transport [Amigo]  potassium ion transport
GO	induction of apoptosis [Amigo]  induction of apoptosis
GO	cell cycle [Amigo]  cell cycle
GO	cell cycle arrest [Amigo]  cell cycle arrest
GO	sensory perception of sound [Amigo]  sensory perception of sound
GO	positive regulation of cell proliferation [Amigo]  positive regulation of cell proliferation
GO	negative regulation of cell growth [Amigo]  negative regulation of cell growth
GO	positive regulation of microtubule polymerization [Amigo]  positive regulation of microtubule polymerization
GO	negative regulation of phosphorylation [Amigo]  negative regulation of phosphorylation
GO	negative regulation of cyclin-dependent protein kinase activity [Amigo]  negative regulation of cyclin-dependent protein kinase activity
GO	autophagic cell death [Amigo]  autophagic cell death
GO	inner ear development [Amigo]  inner ear development
GO	negative regulation of epithelial cell proliferation [Amigo]  negative regulation of epithelial cell proliferation
GO	negative regulation of cell motility [Amigo]  negative regulation of cell motility
BIOCARTA	Influence of Ras and Rho proteins on G1 to S Transition    [Genes]
BIOCARTA	Cyclins and Cell Cycle Regulation    [Genes]
BIOCARTA	CTCF: First Multivalent Nuclear Factor    [Genes]
BIOCARTA	Cell Cycle: G1/S Check Point    [Genes]
BIOCARTA	CDK Regulation of DNA Replication    [Genes]
BIOCARTA	Regulation of p27 Phosphorylation during Cell Cycle Progression    [Genes]
BIOCARTA	PTEN dependent cell cycle arrest and apoptosis    [Genes]
KEGG	Cell cycle
PubGene	CDKN1B
TreeFam	CDKN1B
CTD	1027 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	CDKN1B Related clones (RZPD - Berlin)
	PubMed
PubMed	309 Pubmed reference(s) in LocusLink

Bibliography

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PMID 8637245

Deletions of CDKN1B and ETV6 in acute myeloid leukemia and myelodysplastic syndromes without cytogenetic evidence of 12p abnormalities.

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PMID 9171997

Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.

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PMID 9018244

Molecular analysis of cyclin-dependent kinase inhibitors in human leukemias.

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PMID 9324291

Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas.

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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

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Contributor(s)

Written	05-1998	Chrystele Bilhou-Nabera

Citation

This paper should be referenced as such :

Bilhou-Nabera C . CDKN1B (cyclin-dependent kinase inhibitor 1 B ). Atlas Genet Cytogenet Oncol Haematol. May 1998 . URL : http://AtlasGeneticsOncology.org/Genes/CDKN1BID116.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:22:38 2008