CDKN1B (cyclin-dependent kinase inhibitor 1 B)

1998-05-01   Chrystele Bilhou-Nabera 

Cytogénétique,Laboratoire dHématologie-Pr RAPHAEL, Pav BROCA - 4eme étage, 78 rue du Général Leclerc, 94275 LE KREMLIN-BICETRE, France

Identity

HGNC
LOCATION
12p13.1
IMAGE
Atlas Image
LEGEND
CDK1B (12p3) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
CDKN4,KIP1,MEN1B,MEN4,P27KIP1
FUSION GENES

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

Proteins

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 name
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 name
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 name
primary colorectal carcinomas
Prognosis
CDKN1B is an independent prognostic marker: low levels are significantly correlated with a poor prognosis.

Bibliography

Pubmed IDLast YearTitleAuthors
91719971997Deletions of CDKN1B and ETV6 in acute myeloid leukemia and myelodysplastic syndromes without cytogenetic evidence of 12p abnormalities.Andreasson P et al
90182441997Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer.Catzavelos C et al
93242911997Molecular analysis of cyclin-dependent kinase inhibitors in human leukemias.Hayette S et al
85969541996Translational control of p27Kip1 accumulation during the cell cycle.Hengst L et al
90182451997Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas.Loda M et al
78823091995Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias.Pietenpol JA et al
80332121994Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.Polyak K et al
90182431997Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients.Porter PL et al
86372451996Germline configuration of the p27(Kip1) gene in childhood acute lymphoblastic leukemia (ALL).Seriu T et al
90182301997Cancer prognostics: past, present and p27.Steeg PS et al
80332131994p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21.Toyoshima H et al

Other Information

Locus ID:

NCBI: 1027
MIM: 600778
HGNC: 1785
Ensembl: ENSG00000111276

Variants:

dbSNP: 1027
ClinVar: 1027
TCGA: ENSG00000111276
COSMIC: CDKN1B

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000111276ENST00000228872P46527
ENSG00000111276ENST00000228872Q6I9V6
ENSG00000111276ENST00000396340E7ES52
ENSG00000111276ENST00000442489H7C2T1

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
ErbB signaling pathwayKEGGko04012
Cell cycleKEGGko04110
Prostate cancerKEGGko05215
Chronic myeloid leukemiaKEGGko05220
Small cell lung cancerKEGGko05222
ErbB signaling pathwayKEGGhsa04012
Cell cycleKEGGhsa04110
Pathways in cancerKEGGhsa05200
Prostate cancerKEGGhsa05215
Chronic myeloid leukemiaKEGGhsa05220
Small cell lung cancerKEGGhsa05222
MeaslesKEGGko05162
MeaslesKEGGhsa05162
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
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
FoxO signaling pathwayKEGGhsa04068
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
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
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases activate CITREACTOMER-HSA-5625900
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
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
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
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Signaling by PTK6REACTOMER-HSA-8848021
PTK6 Regulates Cell CycleREACTOMER-HSA-8849470
TP53 Regulates Transcription of Cell Cycle GenesREACTOMER-HSA-6791312
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle ArrestREACTOMER-HSA-6804116
Endocrine resistanceKEGGko01522
Endocrine resistanceKEGGhsa01522

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA448871celecoxibChemicalPathwayassociated22336956

References

Pubmed IDYearTitleCitations
255247982015The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.448
172377712007The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis.353
187083512008MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1.300
176272782007Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation.296
122443022002PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest.272
185210802008MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma.229
122443012002PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization.218
122443032002Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer.177
208183872010A Pumilio-induced RNA structure switch in p27-3' UTR controls miR-221 and miR-222 accessibility.168
244579522014Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1).149

Citation

Chrystele Bilhou-Nabera

CDKN1B (cyclin-dependent kinase inhibitor 1 B)

Atlas Genet Cytogenet Oncol Haematol. 1998-05-01

Online version: http://atlasgeneticsoncology.org/gene/116/cdkn1b-(cyclin-dependent-kinase-inhibitor-1-b)