CDKN2C
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。p18INK4cの名称でも知られる[5][6][7]。
機能 編集
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 編集
出典 編集
- ^ 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 編集
- “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.