CDKN2C
Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene.[1][2][3]
The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to interact with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. Ectopic expression of this gene was shown to suppress the growth of human cells in a manner that appears to correlate with the presence of a wild-type RB1 function. Studies in the knockout mice suggested the roles of this gene in regulating spermatogenesis, as well as in suppressing tumorigenesis. Two alternatively spliced transcript variants of this gene, which encode an identical protein, have been reported.[3]
Interactions
CDKN2C has been shown to interact with Cyclin-dependent kinase 4[4][1] and Cyclin-dependent kinase 6.[4][1][5]
References
- ^ a b c Guan KL, Jenkins CW, Li Y, Nichols MA, Wu X, O'Keefe CL, Matera AG, Xiong Y (Jan 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. doi:10.1101/gad.8.24.2939. PMID 8001816.
- ^ Blais A, Labrie Y, Pouliot F, Lachance Y, Labrie C (Jul 1998). "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. doi:10.1006/bbrc.1998.8497. PMID 9636670.
- ^ a b "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1031.
- ^ a b Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948.
- ^ Jeffrey, P D; Tong L, Pavletich N P (Dec. 2000). "Structural basis of inhibition of CDK–cyclin complexes by INK4 inhibitors". Genes Dev. (UNITED STATES) 14 (24): 3115–25. doi:10.1101/gad.851100. ISSN 0890-9369. PMC 317144. PMID 11124804. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317144.
Further reading
- Serrano M, Hannon GJ, Beach D (1994). "A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4". Nature 366 (6456): 704–7. doi:10.1038/366704a0. PMID 8259215.
- Ghosh PK, Anderson J, Cohen N, et al. (1993). "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. PMID 8397372.
- Simos G, Maison C, Georgatos SD (1996). "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. doi:10.1074/jbc.271.21.12617. PMID 8647873.
- Ragione FD, Russo GL, Oliva A, et al. (1996). "Biochemical characterization of p16INK4- and p18-containing complexes in human cell lines". J. Biol. Chem. 271 (27): 15942–9. doi:10.1074/jbc.271.27.15942. PMID 8663131.
- Lapointe J, Lachance Y, Labrie Y, Labrie C (1996). "A p18 mutant defective in CDK6 binding in human breast cancer cells". Cancer Res. 56 (20): 4586–9. PMID 8840966.
- Venkataramani R, Swaminathan K, Marmorstein R (1998). "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. doi:10.1038/nsb0198-74. PMID 9437433.
- Fåhraeus R, Laín S, Ball KL, Lane DP (1998). "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. doi:10.1038/sj.onc.1201580. PMID 9482104.
- Iolascon A, Giordani L, Moretti A, et al. (1998). "Analysis of CDKN2A, CDKN2B, CDKN2C, and cyclin Ds gene status in hepatoblastoma". Hepatology 27 (4): 989–95. doi:10.1002/hep.510270414. PMID 9537438.
- Noh SJ, Li Y, Xiong Y, Guan KL (1999). "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. PMID 9973200.
- Li J, Byeon IJ, Ericson K, et al. (1999). "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. doi:10.1021/bi982286e. PMID 10074345.
- Schreiber M, Muller WJ, Singh G, Graham FL (1999). "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. doi:10.1038/sj.onc.1202466. PMID 10208428.
- Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16267.
- Korshunov A, Golanov A (2002). "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. doi:10.1043/0003-9985(2002)126<0042:IAOPAP>2.0.CO;2. PMID 11800646.
- Blais A, Monté D, Pouliot F, Labrie C (2002). "Regulation of the human cyclin-dependent kinase inhibitor p18INK4c by the transcription factors E2F1 and Sp1". J. Biol. Chem. 277 (35): 31679–93. doi:10.1074/jbc.M204554200. PMID 12077144.
- Arcellana-Panlilio MY, Egeler RM, Ujack E, et al. (2002). "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. doi:10.1002/gcc.10108. PMID 12203782.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Komata T, Kanzawa T, Takeuchi H, et al. (2004). "Antitumour effect of cyclin-dependent kinase inhibitors (p16INK4A, p18INK4C, p19INK4D, p21WAF1/CIP1 and p27KIP1) on malignant glioma cells". Br. J. Cancer 88 (8): 1277–80. doi:10.1038/sj.bjc.6600862. PMC 2747579. PMID 12698196. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2747579.
- Sánchez-Aguilera A, Delgado J, Camacho FI, et al. (2004). "Silencing of the p18INK4c gene by promoter hypermethylation in Reed-Sternberg cells in Hodgkin lymphomas". Blood 103 (6): 2351–7. doi:10.1182/blood-2003-07-2356. PMID 14645011.
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PDB gallery
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1bu9: SOLUTION STRUCTURE OF P18-INK4C, 21 STRUCTURES
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1g3n: STRUCTURE OF A P18(INK4C)-CDK6-K-CYCLIN TERNARY COMPLEX
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1ihb: CRYSTAL STRUCTURE OF P18-INK4C(INK6)
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1mx2: Structure of F71N mutant of p18INK4c
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1mx4: Structure of p18INK4c (F82Q)
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1mx6: Structure of p18INK4c (F92N)
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| Cyclin |
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| CDK |
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| CDK inhibitor |
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| P53 p63 p73 family |
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Phases and
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B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)
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