| Written | 1998-05 | Chrystele Bilhou-Nabera |
| Cytogénétique,Laboratoire d'Hématologie-Pr RAPHAEL, Pav BROCA - 4eme étage, 78 rue du Général Leclerc, 94275 LE KREMLIN-BICETRE, France |
| Identity |
| Alias_names | cyclin-dependent kinase inhibitor 1B (p27 |
| Alias_symbol (synonym) | KIP1 |
| P27KIP1 | |
| Other alias | |
| HGNC (Hugo) | CDKN1B |
| LocusID (NCBI) | 1027 |
| Atlas_Id | 116 |
| Location | 12p13.1 [Link to chromosome band 12p13] |
| Location_base_pair | Starts at 12717270 and ends at 12722382 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 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Cancer prognostics: past, present and p27. |
| Steeg PS, Abrams JS |
| Nature medicine. 1997 ; 3 (2) : 152-154. |
| PMID 9018230 |
| 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 |
| 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) [ 1 ] |
|
t(12;12)(p13;p13) ETV6/CDKN1B
|
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ] |
|
Esophagus: Barrett's esophagus, dysplasia and adenocarcinoma
Neuro-Endocrine/Endocrine system: Carcinoid tumors Prostate tumors: an overview APOLD1/CDKN1B (12p13) |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Tue Nov 6 12:06:24 CET 2018 |
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