サイクリン依存性キナーゼ4
WordNet
- relying on or requiring a person or thing for support, supply, or what is needed; "dependent children"; "dependent on moisture"
- addicted to a drug (同)dependant, drug-addicted, hooked, strung-out
- contingent on something else (同)dependant, qualified
- (of a clause) unable to stand alone syntactically as a complete sentence; "a subordinate (or dependent) clause functions as a noun or adjective or adverb within a sentence" (同)subordinate
- an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
- the basic unit of money in Papua New Guinea
PrepTutorEJDIC
- 『頼っている』,依存している,従属している / 扶養される人(家族)
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/03/11 14:46:15」(JST)
[Wiki en表示]
| CDK4 |
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| Available structures |
| PDB |
Ortholog search: PDBe RCSB |
| List of PDB id codes |
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2W96, 2W99, 2W9F, 2W9Z, 3G33, 5FWL, 5FWM, 5FWK
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| Identifiers |
| Aliases |
CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4 |
| External IDs |
OMIM: 123829 MGI: 88357 HomoloGene: 55429 GeneCards: CDK4 |
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| Targeted by Drug |
| alvocidib, palbociclib[1] |
| Gene ontology |
| Molecular function |
• transferase activity
• nucleotide binding
• protein kinase activity
• cyclin-dependent protein serine/threonine kinase activity
• protein complex binding
• kinase activity
• protein serine/threonine kinase activity
• cyclin-dependent protein serine/threonine kinase regulator activity
• protein binding
• ATP binding
• cyclin binding
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| Cellular component |
• cytoplasm
• cytosol
• cyclin-dependent protein kinase holoenzyme complex
• nuclear membrane
• membrane
• transcription factor complex
• bicellular tight junction
• nucleoplasm
• nucleolus
• perinuclear region of cytoplasm
• chromatin
• nucleus
• protein complex
• cyclin D2-CDK4 complex
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| Biological process |
• phosphorylation
• response to testosterone
• positive regulation of fibroblast proliferation
• response to hyperoxia
• G1/S transition of mitotic cell cycle
• positive regulation of translation
• regulation of cell cycle
• cell division
• negative regulation of cell cycle arrest
• protein phosphorylation
• lens development in camera-type eye
• regulation of cell proliferation
• response to lead ion
• circadian rhythm
• animal organ regeneration
• positive regulation of cell proliferation
• positive regulation of cell size
• positive regulation of apoptotic process
• regulation of gene expression
• cell cycle
• positive regulation of G2/M transition of mitotic cell cycle
• response to toxic substance
• response to drug
• positive regulation of cell cycle
• regulation of protein kinase activity
• signal transduction
• multicellular organism development
• response to organic substance
• cellular response to insulin stimulus
• regulation of multicellular organism growth
• regulation of insulin receptor signaling pathway
• regulation of lipid biosynthetic process
• regulation of lipid catabolic process
• adipose tissue development
• cellular response to lipopolysaccharide
• cellular response to interleukin-4
• cellular response to phorbol 13-acetate 12-myristate
• cellular response to ionomycin
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| Sources:Amigo / QuickGO |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
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| Ensembl |
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| UniProt |
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| RefSeq (mRNA) |
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| RefSeq (protein) |
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| Location (UCSC) |
Chr 12: 57.75 – 57.76 Mb |
Chr 10: 127.06 – 127.07 Mb |
| PubMed search |
[2] |
[3] |
| Wikidata |
| View/Edit Human |
View/Edit Mouse |
Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene. CDK4 is a member of the cyclin-dependent kinase family.
Contents
- 1 Function
- 2 Clinical significance
- 3 Interactions
- 4 References
- 5 Further reading
- 6 External links
Function
The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16INK4a. This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb).[4] Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G1phase. Hypophosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.[5]
Clinical significance
Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported.[4]
It is regulated by Cyclin D.
Inhibitors
Palbociclib is US FDA approved (Feb 2015) for estrogen receptor-positive advanced breast cancer.[6]
See also CDK inhibitor for inhibitors of various CDKs.
Interactions
Cyclin-dependent kinase 4 has been shown to interact with:
- CDC37,[7][8][9][10]
- CDKN1B,[11][12]
- CDKN2B,[13][14]
- CDKN2C,[7][15]
- CEBPA,[16]
- CCND1,[11][12][17][18][19][20]
- CCND3,[11][13][21][22]
- DBNL,[7]
- MyoD,[23][24]
- P16,[7][17][18][20][25][26]
- PCNA,[18][27] and
- SERTAD1.[17][26]
Overview of signal transduction pathways involved in apoptosis. (CDK4 in the (pink) nucleus)
References
- ^ "Drugs that physically interact with Cyclin dependent kinase 4 view/edit references on wikidata".
- ^ "Human PubMed Reference:".
- ^ "Mouse PubMed Reference:".
- ^ a b "Entrez Gene: CDK4 cyclin-dependent kinase 4".
- ^ http://www.uniprot.org/uniprot/P11802.
- ^ "FDA Approves Palbociclib for Metastatic Breast Cancer". OncLive. 3 Feb 2015.
- ^ a b c d Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
- ^ Dai K, Kobayashi R, Beach D (1996). "Physical interaction of mammalian CDC37 with CDK4". J. Biol. Chem. 271 (36): 22030–4. doi:10.1074/jbc.271.36.22030. PMID 8703009.
- ^ Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, Draetta GF, Gyuris J (1997). "Interaction between Cdc37 and Cdk4 in human cells". Oncogene. 14 (16): 1999–2004. doi:10.1038/sj.onc.1201036. PMID 9150368.
- ^ Stepanova L, Leng X, Parker SB, Harper JW (1996). "Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4". Genes Dev. 10 (12): 1491–502. doi:10.1101/gad.10.12.1491. PMID 8666233.
- ^ a b c Lin J, Jinno S, Okayama H (2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene. 20 (16): 2000–9. doi:10.1038/sj.onc.1204375. PMID 11360184.
- ^ a b Cariou S, Donovan JC, Flanagan WM, Milic A, Bhattacharya N, Slingerland JM (2000). "Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells". Proc. Natl. Acad. Sci. U.S.A. 97 (16): 9042–6. doi:10.1073/pnas.160016897. PMC 16818. PMID 10908655.
- ^ a b Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- ^ Ghavidel A, Cagney G, Emili A (2005). "A skeleton of the human protein interactome". Cell. 122 (6): 830–2. doi:10.1016/j.cell.2005.09.006.
- ^ Guan KL, Jenkins CW, Li Y, Nichols MA, Wu X, O'Keefe CL, Matera AG, Xiong Y (1994). "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.
- ^ Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler WJ, Timchenko NA (2001). "C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4". Mol. Cell. 8 (4): 817–28. doi:10.1016/S1097-2765(01)00366-5. PMID 11684017.
- ^ a b c Sugimoto M, Nakamura T, Ohtani N, Hampson L, Hampson IN, Shimamoto A, Furuichi Y, Okumura K, Niwa S, Taya Y, Hara E (1999). "Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1)". Genes Dev. 13 (22): 3027–33. doi:10.1101/gad.13.22.3027. PMC 317153. PMID 10580009.
- ^ a b c Nasmyth K, Hunt T (1993). "Cell cycle. Dams and sluices". Nature. 366 (6456): 634–5. doi:10.1038/366634a0. PMID 8259207.
- ^ Taulés M, Rius E, Talaya D, López-Girona A, Bachs O, Agell N (1998). "Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". J. Biol. Chem. 273 (50): 33279–86. doi:10.1074/jbc.273.50.33279. PMID 9837900.
- ^ a b Coleman KG, Wautlet BS, Morrissey D, Mulheron J, Sedman SA, Brinkley P, Price S, Webster KR (1997). "Identification of CDK4 sequences involved in cyclin D1 and p16 binding". J. Biol. Chem. 272 (30): 18869–74. doi:10.1074/jbc.272.30.18869. PMID 9228064.
- ^ Arsenijevic T, Degraef C, Dumont JE, Roger PP, Pirson I (2004). "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". Biochem. J. 378 (Pt 2): 673–9. doi:10.1042/BJ20031765. PMC 1223988. PMID 14641107.
- ^ Zhang Q, Wang X, Wolgemuth DJ (1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology. 140 (6): 2790–800. doi:10.1210/endo.140.6.6756. PMID 10342870.
- ^ Zhang JM, Zhao X, Wei Q, Paterson BM (1999). "Direct inhibition of G(1) cdk kinase activity by MyoD promotes myoblast cell cycle withdrawal and terminal differentiation". EMBO J. 18 (24): 6983–93. doi:10.1093/emboj/18.24.6983. PMC 1171761. PMID 10601020.
- ^ Zhang JM, Wei Q, Zhao X, Paterson BM (1999). "Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4". EMBO J. 18 (4): 926–33. doi:10.1093/emboj/18.4.926. PMC 1171185. PMID 10022835.
- ^ Fåhraeus R, Paramio JM, Ball KL, Laín S, Lane DP (1996). "Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A". Curr. Biol. 6 (1): 84–91. doi:10.1016/S0960-9822(02)00425-6. PMID 8805225.
- ^ a b Li J, Melvin WS, Tsai MD, Muscarella P (2004). "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". Biochemistry. 43 (14): 4394–9. doi:10.1021/bi035601s. PMID 15065884.
- ^ Xiong Y, Zhang H, Beach D (1993). "Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation". Genes Dev. 7 (8): 1572–83. doi:10.1101/gad.7.8.1572. PMID 8101826.
Further reading
- Hanks SK (1987). "Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family". Proc. Natl. Acad. Sci. U.S.A. 84 (2): 388–92. doi:10.1073/pnas.84.2.388. PMC 304212. PMID 2948189.
- Hall M, Bates S, Peters G (1995). "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. PMID 7478582.
- Tassan JP, Jaquenoud M, Léopold P, et al. (1995). "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S.A. 92 (19): 8871–5. doi:10.1073/pnas.92.19.8871. PMC 41069. PMID 7568034.
- Mitchell EL, White GR, Santibanez-Koref MF, et al. (1995). "Mapping of gene loci in the Q13-Q15 region of chromosome 12". Chromosome Res. 3 (4): 261–2. doi:10.1007/BF00713052. PMID 7606365.
- Wölfel T, Hauer M, Schneider J, et al. (1995). "A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma". Science. 269 (5228): 1281–4. doi:10.1126/science.7652577. PMID 7652577.
- Hirai H, Roussel MF, Kato JY, et al. (1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Mol. Cell. Biol. 15 (5): 2672–81. PMC 230497. PMID 7739547.
- Chan FK, Zhang J, Cheng L, et al. (1995). "Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4". Mol. Cell. Biol. 15 (5): 2682–8. PMC 230498. PMID 7739548.
- Guan KL, Jenkins CW, Li Y, et al. (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.
- Kato JY, Matsuoka M, Strom DK, Sherr CJ (1994). "Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase". Mol. Cell. Biol. 14 (4): 2713–21. doi:10.1128/MCB.14.4.2713. PMC 358637. PMID 8139570.
- Khatib ZA, Matsushime H, Valentine M, et al. (1993). "Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas". Cancer Res. 53 (22): 5535–41. PMID 8221695.
- 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.
- Demetrick DJ, Zhang H, Beach DH (1994). "Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes". Cytogenet. Cell Genet. 66 (1): 72–4. doi:10.1159/000133669. PMID 8275715.
- Kato J, Matsushime H, Hiebert SW, et al. (1993). "Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4". Genes Dev. 7 (3): 331–42. doi:10.1101/gad.7.3.331. PMID 8449399.
- Zuo L, Weger J, Yang Q, et al. (1996). "Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma". Nat. Genet. 12 (1): 97–9. doi:10.1038/ng0196-97. PMID 8528263.
- Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
- Knudsen ES, Wang JY (1996). "Differential regulation of retinoblastoma protein function by specific Cdk phosphorylation sites". J. Biol. Chem. 271 (14): 8313–20. doi:10.1074/jbc.271.14.8313. PMID 8626527.
- Poon RY, Jiang W, Toyoshima H, Hunter T (1996). "Cyclin-dependent kinases are inactivated by a combination of p21 and Thr-14/Tyr-15 phosphorylation after UV-induced DNA damage". J. Biol. Chem. 271 (22): 13283–91. doi:10.1074/jbc.271.22.13283. PMID 8662825.
- Stepanova L, Leng X, Parker SB, Harper JW (1996). "Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4". Genes Dev. 10 (12): 1491–502. doi:10.1101/gad.10.12.1491. PMID 8666233.
- Dai K, Kobayashi R, Beach D (1996). "Physical interaction of mammalian CDC37 with CDK4". J. Biol. Chem. 271 (36): 22030–4. doi:10.1074/jbc.271.36.22030. PMID 8703009.
- Fåhraeus R, Paramio JM, Ball KL, et al. (1996). "Inhibition of pRb phosphorylation and cell-cycle progression by a 20-residue peptide derived from p16CDKN2/INK4A". Curr. Biol. 6 (1): 84–91. doi:10.1016/S0960-9822(02)00425-6. PMID 8805225.
External links
- Cyclin-Dependent Kinase 4 at the US National Library of Medicine Medical Subject Headings (MeSH)
- CDK4 human gene location in the UCSC Genome Browser.
- CDK4 human gene details in the UCSC Genome Browser.
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Cell cycle proteins
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| Cyclin |
- A (A1, A2)
- B (B1, B2, B3)
- D (D1, D2, D3)
- E (E1, E2)
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| CDK |
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- CDK-activating kinase
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| CDK inhibitor |
- INK4a/ARF (p14arf/p16, p15, p18, p19)
- cip/kip (p21, p27, p57)
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| P53 p63 p73 family |
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| Other |
- Cdc2
- Cdc25
- Cdc42
- Cellular apoptosis susceptibility protein
- E2F
- Maturation promoting factor
- Wee
- Cullin (CUL7)
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Phases and
checkpoints |
| Interphase |
- G1 phase
- S phase
- G2 phase
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| M phase |
- Mitosis (Preprophase
- Prophase
- Prometaphase
- Metaphase
- Anaphase
- Telophase)
- Cytokinesis
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| Cell cycle checkpoints |
- Restriction point
- Spindle checkpoint
- Postreplication checkpoint
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| Other cellular phases |
- Apoptosis
- G0 phase
- Meiosis
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Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)
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Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)
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Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)
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| Polo kinase (EC 2.7.11.21) |
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| Cyclin-dependent kinase (EC 2.7.11.22) |
- CDK1
- CDK2
- CDKL2
- CDK3
- CDK4
- CDK5
- CDKL5
- CDK6
- CDK7
- CDK8
- CDK9
- CDK10
- CDK12
- CDC2L5
- PCTK1
- PCTK2
- PCTK3
- PFTK1
- CDC2L1
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| (RNA-polymerase)-subunit kinase (EC 2.7.11.23) |
- RPS6KA5
- RPS6KA4
- P70S6 kinase
- P70-S6 Kinase 1
- RPS6KB2
- RPS6KA2
- RPS6KA3
- RPS6KA1
- RPS6KC1
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| Mitogen-activated protein kinase (EC 2.7.11.24) |
- Extracellular signal-regulated
- MAPK1
- MAPK3
- MAPK4
- MAPK6
- MAPK7
- MAPK12
- MAPK15
- C-Jun N-terminal
- P38 mitogen-activated protein
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| MAP3K (EC 2.7.11.25) |
- MAP kinase kinase kinases
- MAP3K1
- MAP3K2
- MAP3K3
- MAP3K4
- MAP3K5
- MAP3K6
- MAP3K7
- MAP3K8
- RAFs
- MLKs
- MAP3K12
- MAP3K13
- MAP3K9
- MAP3K10
- MAP3K11
- MAP3K7
- ZAK
- CDC7
- MAP3K14
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| Tau-protein kinase (EC 2.7.11.26) |
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| (acetyl-CoA carboxylase) kinase (EC 2.7.11.27) |
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| Tropomyosin kinase (EC 2.7.11.28) |
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| Low-density-lipoprotein receptor kinase (EC 2.7.11.29) |
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| Receptor protein serine/threonine kinase (EC 2.7.11.30) |
- Bone morphogenetic protein receptors
- BMPR1
- BMPR1A
- BMPR1B
- BMPR2
- ACVR1
- ACVR1B
- ACVR1C
- ACVR2A
- ACVR2B
- ACVRL1
- Anti-Müllerian hormone receptor
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Dual-specificity kinases (EC 2.7.12)
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| MAP2K |
- MAP2K1
- MAP2K2
- MAP2K3
- MAP2K4
- MAP2K5
- MAP2K6
- MAP2K7
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Enzymes
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| Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
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| Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
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| Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
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| Kinetics |
- Enzyme kinetics
- Eadie–Hofstee diagram
- Hanes–Woolf plot
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
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| Types |
- EC1 Oxidoreductases (list)
- EC2 Transferases (list)
- EC3 Hydrolases (list)
- EC4 Lyases (list)
- EC5 Isomerases (list)
- EC6 Ligases (list)
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UpToDate Contents
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English Journal
- Intravesical Instillation of c-MYC Inhibitor KSI-3716 Suppresses Orthotopic Bladder Tumor Growth.
- Jeong KC1, Kim KT2, Seo HH3, Shin SP3, Ahn KO1, Ji MJ2, Park WS4, Kim IH5, Lee SJ6, Seo HK7.Author information 1Biomolecular Function Research Branch, National Cancer Center, Gyeonggi-do, Republic of Korea.2Molecular Epidemiology Branch, National Cancer Center, Gyeonggi-do, Republic of Korea.3Genitourinary Cancer Branch, National Cancer Center, Gyeonggi-do, Republic of Korea.4Center for Prostate Cancer, National Cancer Center, Gyeonggi-do, Republic of Korea.5Molecular Imaging and Therapy Branch, National Cancer Center, Gyeonggi-do, Republic of Korea.6Genitourinary Cancer Branch, National Cancer Center, Gyeonggi-do, Republic of Korea. Electronic address: leesj@ncc.re.kr.7Center for Prostate Cancer, National Cancer Center, Gyeonggi-do, Republic of Korea. Electronic address: seohk@ncc.re.kr.AbstractPURPOSE: c-MYC is a promising target for cancer therapy but its use is restricted by unwanted, devastating side effects. We explored whether intravesical instillation of the c-MYC inhibitor KSI-3716 could suppress tumor growth in murine orthotopic bladder xenografts.
- The Journal of urology.J Urol.2014 Feb;191(2):510-8. doi: 10.1016/j.juro.2013.07.019. Epub 2013 Jul 17.
- PURPOSE: c-MYC is a promising target for cancer therapy but its use is restricted by unwanted, devastating side effects. We explored whether intravesical instillation of the c-MYC inhibitor KSI-3716 could suppress tumor growth in murine orthotopic bladder xenografts.MATERIALS AND METHODS: The small
- PMID 23872029
- Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-related Kinase 5 (ARK5).
- Reddy MV, Akula B, Cosenza SC, Athuluridivakar S, Mallireddigari MR, Pallela VR, Billa VK, Subbaiah DR, Bharathi EV, Vasquez-Del Carpio R, Padgaonkar A, Baker SJ, Reddy EP.AbstractThe success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for developing multi kinase inhibitors with low toxicity profiles. With this goal in mind, we analyzed more than 150 novel cyano pyridopyrimidine compounds and identified structure activity relationship trends that can be exploited in the design of potent kinase inhibitors. One compound, 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) was found to be the most active, inducing apoptosis of tumor cells at a concentration of approximately 30-100nM. In vitro kinase profiling revealed that 7x is a multi-kinase inhibitor with potent inhibitory activity against the CDK4/CYCLIN D1 and ARK5 kinases. Here, we report the synthesis, structure activity relationship, kinase inhibitory profile, in vitro cytotoxicity and in vivo tumor regression studies by this lead compound.
- Journal of medicinal chemistry.J Med Chem.2014 Jan 13. [Epub ahead of print]
- The success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for de
- PMID 24417566
- Current management options for liposarcoma and challenges for the future.
- Kollár A, Benson C.Author information The Royal Marsden Hospital, Sarcoma Unit, Fulham Road, SW3 6JJ, London, UK.AbstractLiposarcoma (LS) represents one of the most common soft tissue sarcomas. There are three major subtypes, namely, well/dedifferentiated, myxoid/round cell and pleomorphic LS. In general, LS is known to be a relatively chemo-resistant sarcoma subtype with the exception of the myxoid variant. Conventional chemotherapy with doxorubicin and ifosfamide represents the mainstay of systemic treatment in the first line. Other active cytotoxic agents include gemcitabine and docetaxel and the marine-derived compounds trabectedin. Recent progress in molecular diagnostics of each single LS subtype has improved the knowledge of the molecular characteristics and has led to two recent treatment targets: the amplification of mouse double minute 2 homolog and cyclin-dependent kinase-4 in well- and dedifferentiated LS. Thus far, only early-phase trials are reported and no new drugs have been introduced in daily clinical practice. The focus of this review is on current systemic treatment options, including novel strategies.
- Expert review of anticancer therapy.Expert Rev Anticancer Ther.2014 Jan 8. [Epub ahead of print]
- Liposarcoma (LS) represents one of the most common soft tissue sarcomas. There are three major subtypes, namely, well/dedifferentiated, myxoid/round cell and pleomorphic LS. In general, LS is known to be a relatively chemo-resistant sarcoma subtype with the exception of the myxoid variant. Conventio
- PMID 24397249
Japanese Journal
- 乳がん領域における開発中の薬剤 : CDK4/6阻害剤 (特集 早期乳がんおよび進行乳がんに対する新しい標準治療の開発)
- Sulforaphane down-regulates SKP2 to stabilize p27^<KIP1> for inducing antiproliferation in human colon adenocarcinoma cells(GENETICS, MOLECULAR BIOLOGY, AND GENE ENGINEERING)
- Chung Yuan-Kai,Or Richard Chi-Hung,Lu Chien-Hsing,Ouyang Wei-Ting,Yang Shu-Yi,Change Chia-Che
- Journal of bioscience and bioengineering 119(1), 35-42, 2015-01
- … The oncoprotein SKP2 is a key component of the SKP1-CULLIN1-F-box (SCF) E3 ligase complex and is responsible for directing SCF-mediated degradation of cyclin-dependent kinase inhibitor p27^<KIP1> …
- NAID 110009892230
- Farnesoid X receptor knockdown provides significant growth inhibition in hepatocellular carcinoma cells while it does not interfere with the proliferation of primary human hepatocyte-derived cells
- Fujino Tomofumi,Maruko-Ohtake Akiko,Ohtake Yosuke,Kobayashi Tomonori,Ando Ken,Takeuchi Airi,Ohkubo Yasuhito,Hayakawa Makio
- The Journal of Toxicological Sciences 40(4), 501-508, 2015
- … Here, we show that knockdown of the farnesoid X receptor (FXR) effectively suppresses the proliferation of human hepatocellular carcinoma cell lines HepG2 and HLE accompanied by elevated expression of cyclin-dependent kinase (CDK) inhibitor p16/INK4a and p21/Cip1 proteins. …
- NAID 130005087442
Related Links
- Cyclin-dependent kinase 4 is part of the cyclin-dependent kinase family. The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe ...
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- 英
- cyclin-dependent kinase 4
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- 関
- depend、dependence、dependency、dependently
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キナーゼ カイネース リン酸化酵素 phosphoenzyme phosphotransferase
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