CDKN1B (cyclin-dependent kinase inhibitor 1 B)
1998-05-01 Chrystele Bilhou-Nabera AffiliationCytogénétique,Laboratoire dHématologie-Pr RAPHAEL, Pav BROCA - 4eme étage, 78 rue du Général Leclerc, 94275 LE KREMLIN-BICETRE, France
Identity
HGNC
LOCATION
12p13.1
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9171997 | 1997 | Deletions of CDKN1B and ETV6 in acute myeloid leukemia and myelodysplastic syndromes without cytogenetic evidence of 12p abnormalities. | Andreasson P et al |
| 9018244 | 1997 | Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer. | Catzavelos C et al |
| 9324291 | 1997 | Molecular analysis of cyclin-dependent kinase inhibitors in human leukemias. | Hayette S et al |
| 8596954 | 1996 | Translational control of p27Kip1 accumulation during the cell cycle. | Hengst L et al |
| 9018245 | 1997 | Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. | Loda M et al |
| 7882309 | 1995 | Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias. | Pietenpol JA et al |
| 8033212 | 1994 | Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. | Polyak K et al |
| 9018243 | 1997 | Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. | Porter PL et al |
| 8637245 | 1996 | Germline configuration of the p27(Kip1) gene in childhood acute lymphoblastic leukemia (ALL). | Seriu T et al |
| 9018230 | 1997 | Cancer prognostics: past, present and p27. | Steeg PS et al |
| 8033213 | 1994 | p27, 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000111276 | ENST00000228872 | P46527 |
| ENSG00000111276 | ENST00000228872 | Q6I9V6 |
| ENSG00000111276 | ENST00000396340 | E7ES52 |
| ENSG00000111276 | ENST00000442489 | H7C2T1 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA448871 | celecoxib | Chemical | Pathway | associated | 22336956 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38211530 | 2024 | UBE4B regulates p27 expression in A549 NSCLC cells through regulating the interaction of HuR and the p27 5' UTR. | 0 |
| 38301893 | 2024 | The E3 ligase SMURF1 stabilizes p27 via UbcH7 catalyzed K29-linked ubiquitin chains to promote cell migration SMURF1-UbcH7 K29 ubiquitination of p27 and cell migration. | 1 |
| 38211530 | 2024 | UBE4B regulates p27 expression in A549 NSCLC cells through regulating the interaction of HuR and the p27 5' UTR. | 0 |
| 38301893 | 2024 | The E3 ligase SMURF1 stabilizes p27 via UbcH7 catalyzed K29-linked ubiquitin chains to promote cell migration SMURF1-UbcH7 K29 ubiquitination of p27 and cell migration. | 1 |
| 36256846 | 2023 | Germline CDKN1B variant type and site are associated with phenotype in MEN4. | 2 |
| 36334246 | 2023 | Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism. | 3 |
| 36638271 | 2023 | LncRNA LIMp27 Regulates the DNA Damage Response through p27 in p53-Defective Cancer Cells. | 3 |
| 36792756 | 2023 | PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B. | 5 |
| 36825757 | 2023 | Knockdown of UBE2I inhibits tumorigenesis and enhances chemosensitivity of cholangiocarcinoma via modulating p27kip1 nuclear export. | 1 |
| 37762128 | 2023 | Large HBV Surface Protein-Induced Unfolded Protein Response Dynamically Regulates p27 Degradation in Hepatocellular Carcinoma Progression. | 0 |
| 37991262 | 2023 | MicroRNA-221-3p promotes post-burn HUVEC proliferation, migration, and angiogenesis by regulating CDKN1B. | 0 |
| 36256846 | 2023 | Germline CDKN1B variant type and site are associated with phenotype in MEN4. | 2 |
| 36334246 | 2023 | Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism. | 3 |
| 36638271 | 2023 | LncRNA LIMp27 Regulates the DNA Damage Response through p27 in p53-Defective Cancer Cells. | 3 |
| 36792756 | 2023 | PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B. | 5 |
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)
