CDKN2B

CDKN2B（cyclin dependent kinase inhibitor 2B）は、ヒトではCDKN2B遺伝子によってコードされるタンパク質である。p15INK4bまたはMTS2（multiple tumor suppressor 2）の名称でも知られる。 CDKN2B遺伝子はがん抑制遺伝子CDKN2Aに隣接して位置する。この領域はさまざまな種類のがんで高頻度で変異、欠失、調節異常がみられる。この遺伝子はp15INK4bとして知られるサイクリン依存性キナーゼ阻害因子をコードし、CDK4またはCDK6と複合体を形成して、サイクリンDによるCDKの活性化を防ぐ。そのため、細胞周期のG1期の進行を阻害する細胞成長調節因子として機能する。この遺伝子の発現はTGF-βによって急激に誘導されることから、TGF-βによる成長阻害に関与していることが示唆される。選択的スプライシングによる2種類の転写産物が存在し、コードされるタンパク質はN末端配列は共通であるが、C末端が完全に異なる。 CDKN2B遺伝子の産物であるp15は、CDK4と相互作用することが示されている。 ^ a b c GRCh38: Ensembl release 89: ENSG00000147883 - Ensembl, May 2017 ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000073802 - Ensembl, May 2017 ^ Human PubMed Reference: ^ Mouse PubMed Reference: ^ “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.  ^ a b “Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)”. 2021年12月3日閲覧。 ^ “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. PMC 5759028. PMID 28892048. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759028/.  ^ “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. PMC 2743558. PMID 18185590. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743558/.  ^ “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.  ^ “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. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070.  “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. 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. PMC 232094. PMID 9111314. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC232094/.  “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.  “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. PMC 2144649. PMID 10892805. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2144649/.  “DNA cloning using in vitro site-specific recombination”. Genome Research 10 (11): 1788–95. (November 2000). doi:10.1101/gr.143000. PMC 310948. PMID 11076863. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC310948/.  “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. PMID 11692873  “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.