CDKN2B

Cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)
Identifiers
Symbols	CDKN2B; CDK4I; INK4B; MTS2; P15; TP15; p15INK4b
External IDs	OMIM: 600431 MGI: 104737 HomoloGene: 55859 GeneCards: CDKN2B Gene
Gene Ontology
Molecular function	• cyclin-dependent protein kinase inhibitor activity; • cyclin-dependent protein kinase inhibitor activity; • protein binding; • kinase activity; • protein kinase binding;
Cellular component	• nucleus; • cytoplasm; • cytosol;
Biological process	• regulation of cyclin-dependent protein kinase activity; • G1 phase of mitotic cell cycle; • G2/M transition of mitotic cell cycle; • mitotic cell cycle; • cell cycle arrest; • negative regulation of cell proliferation; • response to organic cyclic compound; • megakaryocyte differentiation; • positive regulation of transforming growth factor beta receptor signaling pathway; • positive regulation of epithelial cell differentiation; • mitotic cell cycle G1/S transition checkpoint; • cellular response to extracellular stimulus; • cellular response to nutrient; • response to cytokine stimulus; • negative regulation of phosphorylation; • negative regulation of epithelial cell proliferation;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

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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]

[edit] Function

This gene lies adjacent to the tumor suppressor gene CDKN2A in a region that is frequently mutated and deleted in a wide variety of tumors. 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 transcript variants of this gene, which encode distinct proteins, have been reported.^[2]

[edit] Interactions

CDKN2B has been shown to interact with Cyclin-dependent kinase 4.^[3]^[4]

[edit] References

^ Hannon GJ, Beach D (Oct 1994). "p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest". Nature 371 (6494): 257–61. doi:10.1038/371257a0. PMID 8078588.
^ ^a ^b "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1030.
^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
^ Stelzl, Ulrich; Worm Uwe, Lalowski Maciej, Haenig Christian, Brembeck Felix H, Goehler Heike, Stroedicke Martin, Zenkner Martina, Schoenherr Anke, Koeppen Susanne, Timm Jan, Mintzlaff Sascha, Abraham Claudia, Bock Nicole, Kietzmann Silvia, Goedde Astrid, Toksöz Engin, Droege Anja, Krobitsch Sylvia, Korn Bernhard, Birchmeier Walter, Lehrach Hans, Wanker Erich E (Sep. 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell (United States) 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. ISSN 0092-8674. PMID 16169070.

[edit] Further reading

Hall M, Bates S, Peters G (1995). "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. PMID 7478582.
Stone S, Dayananth P, Jiang P, et al. (1995). "Genomic structure, expression and mutational analysis of the P15 (MTS2) gene". Oncogene 11 (5): 987–91. PMID 7675459.
Okamoto A, Hussain SP, Hagiwara K, et al. (1995). "Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer". Cancer Res. 55 (7): 1448–51. PMID 7882351.
Jen J, Harper JW, Bigner SH, et al. (1995). "Deletion of p16 and p15 genes in brain tumors". Cancer Res. 54 (24): 6353–8. PMID 7987828.
Guan KL, Jenkins CW, Li Y, et al. (1995). "Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function". Genes Dev. 8 (24): 2939–52. doi:10.1101/gad.8.24.2939. PMID 8001816.
Kamb A, Gruis NA, Weaver-Feldhaus J, et al. (1994). "A cell cycle regulator potentially involved in genesis of many tumor types". Science 264 (5157): 436–40. doi:10.1126/science.8153634. PMID 8153634.
Reynisdóttir I, Massagué J (1997). "The subcellular locations of p15(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2". Genes Dev. 11 (4): 492–503. doi:10.1101/gad.11.4.492. PMID 9042862.
Sandhu C, Garbe J, Bhattacharya N, et al. (1997). "Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B-cdk4 complexes, and inhibits cyclin D1-cdk4 association in human mammary epithelial cells". Mol. Cell. Biol. 17 (5): 2458–67. PMC 232094. PMID 9111314. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=232094.
Iavarone A, Massagué J (1997). "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. doi:10.1038/387417a0. PMID 9163429.
Tsubari M, Tiihonen E, Laiho M (1997). "Cloning and characterization of p10, an alternatively spliced form of p15 cyclin-dependent kinase inhibitor". Cancer Res. 57 (14): 2966–73. PMID 9230210.
Rich JN, Zhang M, Datto MB, et al. (2000). "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". J. Biol. Chem. 274 (49): 35053–8. doi:10.1074/jbc.274.49.35053. PMID 10574984.
Yuan C, Selby TL, Li J, et al. (2000). "Tumor suppressor INK4: refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data". Protein Sci. 9 (6): 1120–8. doi:10.1110/ps.9.6.1120. PMC 2144649. PMID 10892805. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2144649.
Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948.
Staller P, Peukert K, Kiermaier A, et al. (2001). "Repression of p15INK4b expression by Myc through association with Miz-1". Nat. Cell Biol. 3 (4): 392–9. doi:10.1038/35070076. PMID 11283613.
Orlow I, Cordon-Cardo C (2002). "Evaluation of alterations in the tumor suppressor genes INK4A and INK4B in human bladder tumors". Methods Mol. Biol. 179: 43–59. PMID 11692873.
Agiostratidou G, Derventzi A, Gonos ES (2002). "Over-expression of CDKIs p15INK4b, p16INK4a and p21CIP1/WAF1 genes mediate growth arrest in human osteosarcoma cell lines". In Vivo 15 (5): 443–6. PMID 11695244.
Simon M, Park TW, Köster G, et al. (2002). "Alterations of INK4a(p16-p14ARF)/INK4b(p15) expression and telomerase activation in meningioma progression". J. Neurooncol. 55 (3): 149–58. doi:10.1023/A:1013863630293. PMID 11859969.
Scarisbrick JJ, Woolford AJ, Calonje E, et al. (2002). "Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and sezary syndrome". J. Invest. Dermatol. 118 (3): 493–9. doi:10.1046/j.0022-202x.2001.01682.x. PMID 11874489.
Kudoh K, Ichikawa Y, Yoshida S, et al. (2002). "Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer". Int. J. Cancer 99 (4): 579–82. doi:10.1002/ijc.10331. PMID 11992549.

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[pmid8078588-0] Hannon GJ, Beach D (Oct 1994). "p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest". Nature 371 (6494): 257–61. doi:10.1038/371257a0. PMID 8078588.

[entrez-1] "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1030.

[pmid16189514-2] Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.

[pmid16169070-3] Stelzl, Ulrich; Worm Uwe, Lalowski Maciej, Haenig Christian, Brembeck Felix H, Goehler Heike, Stroedicke Martin, Zenkner Martina, Schoenherr Anke, Koeppen Susanne, Timm Jan, Mintzlaff Sascha, Abraham Claudia, Bock Nicole, Kietzmann Silvia, Goedde Astrid, Toksöz Engin, Droege Anja, Krobitsch Sylvia, Korn Bernhard, Birchmeier Walter, Lehrach Hans, Wanker Erich E (Sep. 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell (United States) 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. ISSN 0092-8674. PMID 16169070.

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CDKN2B

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[edit] Function

[edit] Interactions

[edit] References

[edit] Further reading

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