World Library  
Flag as Inappropriate
Email this Article


Article Id: WHEBN0014723274
Reproduction Date:

Title: Cdkn2b  
Author: World Heritage Encyclopedia
Language: English
Subject: CDKN2BAS, Postreplication checkpoint, Cellular apoptosis susceptibility protein, Cyclin B2, Exon junction complex
Publisher: World Heritage Encyclopedia


Cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)
Symbols  ; CDK4I; INK4B; MTS2; P15; TP15; p15INK4b
External IDs GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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 1
  • Interactions 2
  • References 3
  • Further reading 4
  • External links 5


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]


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


  1. ^ Hannon GJ, Beach D (October 1994). "p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest". Nature 371 (6494): 257–61.  
  2. ^ a b "Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)". 
  3. ^ 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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network".  
  4. ^ 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 (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell (United States) 122 (6): 957–68.  

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.  
  • 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.  
  • 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.  
  • Jen J, Harper JW, Bigner SH, et al. (1995). "Deletion of p16 and p15 genes in brain tumors". Cancer Res. 54 (24): 6353–8.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95.  
  • 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.  
  • Orlow I,  
  • 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.  
  • 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.  
  • 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.  
  • 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.  

External links

This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.