CDKN2C

CDKN2C
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
	1BU9, 1G3N, 1IHB, 1MX2, 1MX4, 1MX6
識別子
記号	CDKN2C, INK4C, p18, p18-INK4C, cyclin-dependent kinase inhibitor 2C, cyclin dependent kinase inhibitor 2C
外部ID	OMIM: 603369 MGI: 105388 HomoloGene: 966 GeneCards: CDKN2C
遺伝子の位置 (ヒト)
染色体	1番染色体 (ヒト)
終点	50,974,634 bp
遺伝子の位置 (マウス)
染色体	4番染色体 (マウス)
終点	109,524,386 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	• 細胞周期; • regulation of cyclin-dependent protein serine/threonine kinase activity; • oligodendrocyte differentiation; • negative regulation of phosphorylation; • negative regulation of cell growth; • negative regulation of cell population proliferation; • negative regulation of cyclin-dependent protein serine/threonine kinase activity; • G1/S transition of mitotic cell cycle; • negative regulation of G1/S transition of mitotic cell cycle;
	出典:Amigo / QuickGO
オルソログ
	1031
	12580
	ENSG00000123080
	ENSMUSG00000028551
	P42773
	Q60772
	NM_078626; NM_001262
	NM_001301368; NM_007671
	NP_001253; NP_523240
	NP_001288297; NP_031697
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

CDKN2C（cyclin dependent kinase inhibitor 2C）は、ヒトではCDKN2C遺伝子によってコードされるタンパク質である。p18^INK4cの名称でも知られる^[5]^[6]^[7]。

機能

CDKN2C遺伝子にコードされるタンパク質は、サイクリン依存性キナーゼ阻害因子のINK4ファミリーのメンバーである。このタンパク質はCDK4またはCDK6と相互作用してCDKの活性化を妨げることで、細胞周期のG₁期の進行を制御する細胞成長調節因子として機能する。この遺伝子の異所性発現（英語版）は、野生型のRB1の機能の存在と相関するような形で、ヒト細胞の成長を抑制することが示されている。ノックアウトマウスを用いた研究からは、この遺伝子は精子形成を調節する役割とともに、腫瘍形成を抑制する役割が示唆されている。この遺伝子には選択的スプライシングによる2種類の転写産物が存在するが、同一のタンパク質をコードしている^[7]。

相互作用

CDKN2CはCDK4^[5]^[8]、CDK6^[5]^[8]^[9]と相互作用することが示されている。

出典

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000123080 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028551 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ ^a ^b ^c “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. (January 1995). doi:10.1101/gad.8.24.2939. PMID 8001816.
^ “Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer”. Biochem. Biophys. Res. Commun. 247 (1): 146–53. (July 1998). doi:10.1006/bbrc.1998.8497. PMID 9636670.
^ ^a ^b “Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)”. 2021年12月3日閲覧。
^ ^a ^b “Large-scale mapping of human protein-protein interactions by mass spectrometry”. Mol. Syst. Biol. 3 (1): 89. (2007). doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
^ “Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors”. Genes Dev. 14 (24): 3115–25. (December 2000). doi:10.1101/gad.851100. PMC 317144. PMID 11124804.

関連文献

“A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4”. Nature 366 (6456): 704–7. (1993). Bibcode: 1993Natur.366..704S. doi:10.1038/366704a0. PMID 8259215.
“Expression of the leukemia-associated gene, p18, in normal and malignant tissues; inactivation of expression in a patient with cleaved B cell lymphoma/leukemia”. Oncogene 8 (10): 2869–72. (1993). PMID 8397372.
“Characterization of p18, a component of the lamin B receptor complex and a new integral membrane protein of the avian erythrocyte nuclear envelope”. J. Biol. Chem. 271 (21): 12617–25. (1996). doi:10.1074/jbc.271.21.12617. PMID 8647873.
“Biochemical characterization of p16INK4- and p18-containing complexes in human cell lines”. J. Biol. Chem. 271 (27): 15942–9. (1996). doi:10.1074/jbc.271.27.15942. PMID 8663131.
“A p18 mutant defective in CDK6 binding in human breast cancer cells”. Cancer Res. 56 (20): 4586–9. (1996). PMID 8840966.
“Crystal structure of the CDK4/6 inhibitory protein p18INK4c provides insights into ankyrin-like repeat structure/function and tumor-derived p16INK4 mutations”. Nat. Struct. Biol. 5 (1): 74–81. (1998). doi:10.1038/nsb0198-74. PMID 9437433.
“Characterization of the cyclin-dependent kinase inhibitory domain of the INK4 family as a model for a synthetic tumour suppressor molecule”. Oncogene 16 (5): 587–96. (1998). doi:10.1038/sj.onc.1201580. PMID 9482104.
“Analysis of CDKN2A, CDKN2B, CDKN2C, and cyclin Ds gene status in hepatoblastoma”. Hepatology 27 (4): 989–95. (1998). doi:10.1002/hep.510270414. PMID 9537438.
“Identification of functional elements of p18INK4C essential for binding and inhibition of cyclin-dependent kinase (CDK) 4 and CDK6”. Cancer Res. 59 (3): 558–64. (1999). PMID 9973200.
“Tumor suppressor INK4: determination of the solution structure of p18INK4C and demonstration of the functional significance of loops in p18INK4C and p16INK4A”. Biochemistry 38 (10): 2930–40. (1999). doi:10.1021/bi982286e. PMID 10074345.
“Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity”. Oncogene 18 (9): 1663–76. (1999). doi:10.1038/sj.onc.1202466. PMID 10208428.
“Shotgun sequencing of the human transcriptome with ORF expressed sequence tags”. Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. (2000). Bibcode: 2000PNAS...97.3491D. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
“Immunohistochemical analysis of p18INK4C and p14ARF protein expression in 117 oligodendrogliomas: correlation with tumor grade and clinical outcome”. Arch. Pathol. Lab. Med. 126 (1): 42–8. (2002). doi:10.5858/2002-126-0042-IAOPAP. PMID 11800646.
“Regulation of the human cyclin-dependent kinase inhibitor p18INK4c by the transcription factors E2F1 and Sp1”. J. Biol. Chem. 277 (35): 31679–93. (2002). doi:10.1074/jbc.M204554200. PMID 12077144.
“Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors”. Genes Chromosomes Cancer 35 (2): 176–81. (2002). doi:10.1002/gcc.10108. PMID 12203782.
“Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on malignant glioma cells”. Br. J. Cancer 88 (8): 1277–80. (2003). doi:10.1038/sj.bjc.6600862. PMC 2747579. PMID 12698196.
“Silencing of the p18INK4c gene by promoter hypermethylation in Reed-Sternberg cells in Hodgkin lymphomas”. Blood 103 (6): 2351–7. (2004). doi:10.1182/blood-2003-07-2356. PMID 14645011.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000123080 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028551 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[pmid8001816-5] “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. (January 1995). doi:10.1101/gad.8.24.2939. PMID 8001816.

[pmid9636670-6] “Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer”. Biochem. Biophys. Res. Commun. 247 (1): 146–53. (July 1998). doi:10.1006/bbrc.1998.8497. PMID 9636670.

[entrez-7] “Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)”. 2021年12月3日閲覧。

[pmid17353931-8] “Large-scale mapping of human protein-protein interactions by mass spectrometry”. Mol. Syst. Biol. 3 (1): 89. (2007). doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

[pmid11124804-9] “Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors”. Genes Dev. 14 (24): 3115–25. (December 2000). doi:10.1101/gad.851100. PMC 317144. PMID 11124804.

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