Biology:CDKN2B
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is encoded by the CDKN2B gene in humans.[1][2]
Function
This gene lies adjacent to the tumor suppressor gene CDKN2A in a region that is frequently mutated, deleted, or disregulated in a wide variety of cancer.[3][4][5] This gene encodes a cyclin-dependent kinase inhibitor, also known as p15Ink4b protein, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases by cyclin D, thus the encoded protein functions as a cell growth regulator that inhibits cell cycle G1 progression. The expression of this gene was found to be dramatically induced by TGF beta, which suggested its role in the TGF beta induced growth inhibition. Two alternatively spliced transcripts of this gene encode proteins that share the N-terminal sequence but completely differ in the C-terminus.[2]
Interactions
CDKN2B tumor suppressor gene product p15 has been shown to interact with cyclin-dependent kinase 4.[6][7]
References
- ↑ "p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest". Nature 371 (6494): 257–61. September 1994. doi:10.1038/371257a0. PMID 8078588. Bibcode: 1994Natur.371..257H.
- ↑ 2.0 2.1 "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1030.
- ↑ "CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A". Oncogene 37 (1): 128–138. January 2018. doi:10.1038/onc.2017.316. PMID 28892048.
- ↑ "Germline Mutations in the CDKN2B Tumor Suppressor Gene Predispose to Renal Cell Carcinoma". Cancer Discovery 5 (7): 723–9. July 2015. doi:10.1158/2159-8290.CD-14-1096. PMID 25873077.
- ↑ "Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA". Nature 451 (7175): 202–6. January 2008. doi:10.1038/nature06468. PMID 18185590. Bibcode: 2008Natur.451..202Y.
- ↑ "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- ↑ "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. September 2005. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
Further reading
- "Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to cyclins". Oncogene 11 (8): 1581–8. October 1995. PMID 7478582.
- "Genomic structure, expression and mutational analysis of the P15 (MTS2) gene". Oncogene 11 (5): 987–91. September 1995. PMID 7675459.
- "Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer". Cancer Research 55 (7): 1448–51. April 1995. PMID 7882351.
- "Deletion of p16 and p15 genes in brain tumors". Cancer Research 54 (24): 6353–8. December 1994. PMID 7987828.
- "Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function". Genes & Development 8 (24): 2939–52. December 1994. doi:10.1101/gad.8.24.2939. PMID 8001816.
- "A cell cycle regulator potentially involved in genesis of many tumor types". Science 264 (5157): 436–40. April 1994. doi:10.1126/science.8153634. PMID 8153634. Bibcode: 1994Sci...264..436K. https://zenodo.org/record/1231245.
- "The subcellular locations of p15(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2". Genes & Development 11 (4): 492–503. February 1997. doi:10.1101/gad.11.4.492. PMID 9042862.
- "Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B-cdk4 complexes, and inhibits cyclin D1-cdk4 association in human mammary epithelial cells". Molecular and Cellular Biology 17 (5): 2458–67. May 1997. doi:10.1128/MCB.17.5.2458. PMID 9111314.
- "Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-beta in cells lacking the CDK inhibitor p15". Nature 387 (6631): 417–22. May 1997. doi:10.1038/387417a0. PMID 9163429. Bibcode: 1997Natur.387..417L.
- "Cloning and characterization of p10, an alternatively spliced form of p15 cyclin-dependent kinase inhibitor". Cancer Research 57 (14): 2966–73. July 1997. PMID 9230210.
- "Transforming growth factor-beta-mediated p15(INK4B) induction and growth inhibition in astrocytes is SMAD3-dependent and a pathway prominently altered in human glioma cell lines". The Journal of Biological Chemistry 274 (49): 35053–8. December 1999. doi:10.1074/jbc.274.49.35053. PMID 10574984.
- "Tumor suppressor INK4: refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data". Protein Science 9 (6): 1120–8. June 2000. doi:10.1110/ps.9.6.1120. PMID 10892805.
- "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–95. November 2000. doi:10.1101/gr.143000. PMID 11076863.
- "Repression of p15INK4b expression by Myc through association with Miz-1". Nature Cell Biology 3 (4): 392–9. April 2001. doi:10.1038/35070076. PMID 11283613.
- "Evaluation of alterations in the tumor suppressor genes INK4A and INK4B in human bladder tumors". Gene Probes. Methods Mol. Biol.. 179. 2002. pp. 43–59. doi:10.1385/1-59259-238-4:043. ISBN 1-59259-238-4.
- "Over-expression of CDKIs p15INK4b, p16INK4a and p21CIP1/WAF1 genes mediate growth arrest in human osteosarcoma cell lines". In Vivo 15 (5): 443–6. 2002. PMID 11695244.
- "Alterations of INK4a(p16-p14ARF)/INK4b(p15) expression and telomerase activation in meningioma progression". Journal of Neuro-Oncology 55 (3): 149–58. December 2001. doi:10.1023/A:1013863630293. PMID 11859969.
- "Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and sezary syndrome". The Journal of Investigative Dermatology 118 (3): 493–9. March 2002. doi:10.1046/j.0022-202x.2001.01682.x. PMID 11874489.
- "Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer". International Journal of Cancer 99 (4): 579–82. June 2002. doi:10.1002/ijc.10331. PMID 11992549.
- "Cyclin-Dependent Kinase Inhibitor 2b Controls Fibrosis and Functional Changes in Ischemia-Induced Heart Failure via the BMI1-p15-Rb Signalling Pathway". Canadian Journal of Cardiology 37 (4): 655–664. 2021. doi:10.1016/j.cjca.2020.05.016. PMID 32428618.
External links
- CDKN2B human gene location in the UCSC Genome Browser.
- CDKN2B human gene details in the UCSC Genome Browser.
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