CDKN2B

CDKN2B
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	1D9S
識別子
記号	CDKN2B, CDK4I, INK4B, MTS2, P15, TP15, p15INK4b, cyclin-dependent kinase inhibitor 2B, cyclin dependent kinase inhibitor 2B
外部ID	OMIM: 600431 MGI: 104737 HomoloGene: 55859 GeneCards: CDKN2B
遺伝子の位置 (ヒト)
染色体	9番染色体 (ヒト)
終点	22,009,305 bp
遺伝子の位置 (マウス)
染色体	4番染色体 (マウス)
終点	89,229,276 bp
RNA発現パターン
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• 血漿タンパク結合; • cyclin-dependent protein serine/threonine kinase inhibitor activity; • プロテインキナーゼ結合;
細胞の構成要素	• 細胞質; • 細胞質基質; • 細胞核;
生物学的プロセス	• cellular response to extracellular stimulus; • megakaryocyte differentiation; • positive regulation of transforming growth factor beta receptor signaling pathway; • regulation of cyclin-dependent protein serine/threonine kinase activity; • mitotic cell cycle checkpoint signaling; • 脾臓発生; • cellular response to nutrient; • negative regulation of G1/S transition of mitotic cell cycle; • G2/M transition of mitotic cell cycle; • negative regulation of epithelial cell proliferation; • 細胞周期; • negative regulation of phosphorylation; • positive regulation of transcription by RNA polymerase II; • negative regulation of cell population proliferation; • negative regulation of cyclin-dependent protein serine/threonine kinase activity; • 細胞老化;
	出典:Amigo / QuickGO
オルソログ
	1030
	12579
	ENSG00000147883
	ENSMUSG00000073802
	P42772
	P55271
	NM_078487; NM_004936
	NM_007670
	NP_004927; NP_511042
	NP_031696
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

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。p15^INK4bまたはMTS2（multiple tumor suppressor 2）の名称でも知られる^[5]^[6]。

機能

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^[7]^[8]^[9]。この遺伝子はp15^INK4b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^[6]。

相互作用

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^[10]^[11]。

出典

^ ^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.
^ “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.
^ “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.

関連文献

“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.
“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.
“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.
“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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000147883 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000073802 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[pmid8078588-5] “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.

[entrez-6] “Entrez Gene: CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)”. 2021年12月3日閲覧。

[7] “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.

[8] “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.

[9] “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.

[pmid16189514-10] “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.

[pmid16169070-11] “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.

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