c-myc gene、c-Myc protein

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the 3rd letter of the Roman alphabet (同)c
(music) the keynote of the scale of C major
a general-purpose programing language closely associated with the UNIX operating system
the 13th letter of the Roman alphabet (同)m

PrepTutorEJDIC

carbonの化学記号
Mach number / mark[s] / Monsieur
case[s]

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/12/29 20:46:31」(JST)

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Myc (c-Myc) is a regulator gene that codes for a transcription factor. The protein encoded by this gene is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation.^[1]

A mutated version of Myc is found in many cancers, which causes Myc to be constitutively (persistently) expressed. This leads to the unregulated expression of many genes, some of which are involved in cell proliferation, and results in the formation of cancer.^[1] A common human translocation involving Myc is critical to the development of most cases of Burkitt's Lymphoma.^[2] Malfunctions in Myc have also been found in carcinoma of the cervix, colon, breast, lung and stomach.^[1] Myc is thus viewed as a promising target for anti-cancer drugs.^[3]

In the human genome, Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes^[4] through binding on Enhancer Box sequences (E-boxes) and recruiting histone acetyltransferases (HATs). This means that in addition to its role as a classical transcription factor, Myc also functions to regulate global chromatin structure by regulating histone acetylation both in gene-rich regions and at sites far from any known gene.^[5]

Discovery

Myc gene was first discovered in Burkitt's lymphoma patients. In Burkitt's lymphoma, cancer cells show chromosomal translocations, in which Chromosome 8 is frequently involved. Cloning the break-point of the fusion chromosomes revealed a gene that was similar to myelocytomatosis viral oncogene (v-Myc). Thus, the newfound cellular gene was named c-Myc.

Structure

Myc protein belongs to Myc family of transcription factors, which also includes N-Myc and L-Myc genes. Myc family of transcription factors contain bHLH/LZ (basic Helix-Loop-Helix Leucine Zipper) domain. Myc protein, through its bHLH domain can bind to DNA, while the leucine zipper domain allows the dimerization with its partner Max, another bHLH transcription factor.

Myc mRNA contains an IRES (internal ribosome entry site) that allows the RNA to be translated into protein when 5' cap-dependent translation is inhibited, such as during viral infection.

Function

Myc protein is a transcription factor that activates expression of many genes through binding on consensus sequences (Enhancer Box sequences (E-boxes)) and recruiting histone acetyltransferases (HATs). It can also act as a transcriptional repressor. By binding Miz-1 transcription factor and displacing the p300 co-activator, it inhibits expression of Miz-1 target genes. In addition, myc has a direct role in the control of DNA replication.^[6]

Myc is activated upon various mitogenic signals such as Wnt, Shh and EGF (via the MAPK/ERK pathway). By modifying the expression of its target genes, Myc activation results in numerous biological effects. The first to be discovered was its capability to drive cell proliferation (upregulates cyclins, downregulates p21), but it also plays a very important role in regulating cell growth (upregulates ribosomal RNA and proteins), apoptosis (downregulates Bcl-2), differentiation, and stem cell self-renewal. Myc is a very strong proto-oncogene and it is very often found to be upregulated in many types of cancers. Myc overexpression stimulates gene amplification,^[7] presumably through DNA over-replication.

There have been several studies that have clearly indicated Myc's role in cell competition.^[8]

A major effect of Myc is B cell proliferation.^[9]

c-Myc induces AEG-1 or MTDH gene expression and in turn itself requires AEG-1 oncogene for its expression.

Myc-nick

Myc-nick is a cytoplasmic form of Myc produced by a partial proteolytic cleavage of full-length c-Myc and N-Myc.^[10] Myc cleavage is mediated by the calpain family of calcium-dependent cytosolic proteases.

The cleavage of Myc by calpains is a constitutive process but is enhanced under conditions that require rapid downregulation of Myc levels, such as during terminal differentiation. Upon cleavage, the C-terminus of Myc (containing the DNA binding domain) is degraded, while Myc-nick, the N-terminal segment 298-residue segment remains in the cytoplasm. Myc-nick contains binding domains for histone acetyltransferases and for ubiquitin ligases.

The functions of Myc-nick are currently under investigation, but this new Myc family member was found to regulate cell morphology, at least in part, by interacting with acetyl transferases to promote the acetylation of α-tubulin. Ectopic expression of Myc-nick accelerates the differentiation of committed myoblasts into muscle cells.

Clinical significance

Except for early response genes, Myc universally upregulates gene expression. Furthermore the upregulation is nonlinear. Genes whose expression is already significantly upregulated in the absence of Myc are strongly boosted in the presence of Myc, whereas genes whose expression is low in the absence Myc get only a small boost when Myc is present.^[11]

Inactivation of SUMO-activating enzyme (SAE1 / SAE2) in the presence of Myc hyperactivation results in mitotic catastrophe and cell death in cancer cells. Hence inhibitors of SUMOylation may be a possible treatment for cancer.^[12]

Amplification of the MYC gene was found in a significant number of epithelial ovarian cancer cases.^[13] In TCGA datasets, the amplification of Myc occurs in several cancer types, including breast, colorectal, pancreatic, gastric, and uterine cancers.^[14]

In the experimental transformation process of normal cells into cancer cells, the MYC gene can cooperate with the RAS gene.^[15]^[16]

Animal Models

During the discovery of Myc gene, it was realized that chromosomes that translocate to Chromosome 8 contained immunoglobulin genes at the break-point. Enhancers that normally drive expression of immunoglobin genes now lead to overexpression of Myc proto-oncogene in lymphoma cells. To study the mechanism of tumorigenesis in Burkitt's lymphoma by mimicking expression pattern of Myc in these cancer cells, transgenic mouse models were developed. Myc gene placed under the control of IgM heavy chain enhancer in transgenic mice gives rise to mainly lymphomas. Later on, in order to study effects of Myc in other types of cancer, transgenic mice that overexpress Myc in different tissues (liver, breast) were also made. In all these mouse models overexpression of Myc causes tumorigenesis, illustrating the potency of Myc oncogene.

Interactions

Myc has been shown to interact with:

ACTL6A^[17]
BRCA1^[18]^[19]^[20]^[21]
Bcl-2^[22]
Cyclin T1^[23]
DNMT3A^[24]
EP400^[25]
GTF2I^[26]
HTATIP^[27]
let-7^[28]^[29]^[30]
MAPK1^[22]^[31]^[32]
MAPK8^[33]
MAX^[34]^[35]^[36]^[37]^[38]^[39]^[40]^[41]^[42]^[43]^[44]^[45]^[46]
MLH1^[38]
MYCBP2^[47]
MYCBP^[48]
NMI^[18]
NFYB^[49]
NFYC^[50]
P73^[51]
PCAF^[52]
PFDN5^[53]^[54]
RuvB-like 1^[25]^[17]
SAP130^[52]
SMAD2^[55]
SMAD3^[55]
SMARCA4^[17]^[34]
SMARCB1^[37]
SUPT3H^[52]
TIAM1^[56]
TADA2L^[52]
TAF9^[52]
TFAP2A^[57]
TRRAP^[17]^[52]^[35]^[36]
YY1^[58] and
ZBTB17.^[59]^[60]

Overview of signal transduction pathways involved in apoptosis.

References

^ ^a ^b ^c "Myc". NCBI.
^ Finver SN, Nishikura K, Finger LR, Haluska FG, Finan J, Nowell PC, Croce CM (1988). "Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered".
^ Begley S (2013-01-09). "DNA pioneer James Watson takes aim at cancer establishments". Reuters.
^ Gearhart J, Pashos EE, Prasad MK (2007). "Pluripotency redux--advances in stem-cell research". N. Engl. J. Med. 357 (15): 1469–72. doi:10.1056/NEJMp078126. PMID 17928593.
^ Cotterman R, Jin VX, Krig SR, Lemen JM, Wey A, Farnham PJ, Knoepfler PS (2008). "N-Myc regulates a widespread euchromatic program in the human genome partially independent of its role as a classical transcription factor". Cancer Res. 68 (23): 9654–62. doi:10.1158/0008-5472.CAN-08-1961. PMC 2637654. PMID 19047142.
^ Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, Galloway DA, Gu W, Gautier J, Dalla-Favera R (July 2007). "Non-transcriptional control of DNA replication by c-Myc". Nature 448 (7152): 445–51. doi:10.1038/nature05953. PMID 17597761.
^ Denis N, Kitzis A, Kruh J, Dautry F, Corcos D (August 1991). "Stimulation of methotrexate resistance and dihydrofolate reductase gene amplification by c-myc". Oncogene 6 (8): 1453–7. PMID 1886715.
^ Clavería C, Giovinazzo G, Sierra R, Torres M (August 2013). "Myc-driven endogenous cell competition in the early mammalian embryo". Nature 500 (7460): 39–44. doi:10.1038/nature12389. PMID 23842495.
^ de Alboran IM, O'Hagan RC, Gärtner F, Malynn B, Davidson L, Rickert R, Rajewsky K, DePinho RA, Alt FW (January 2001). "Analysis of C-MYC function in normal cells via conditional gene-targeted mutation". Immunity 14 (1): 45–55. doi:10.1016/S1074-7613(01)00088-7. PMID 11163229.
^ Conacci-Sorrell M, Ngouenet C, Eisenman RN (2010). "Myc-nick: a cytoplasmic cleavage product of Myc that promotes alpha-tubulin acetylation and cell differentiation". Cell 142 (3): 480–93. doi:10.1016/j.cell.2010.06.037. PMC 2923036. PMID 20691906.
^ Nie Z, Hu G, Wei G, Cui K, Yamane A, Resch W, Wang R, Green DR, Tessarollo L, Casellas R, Zhao K, Levens D (September 2012). "c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells". Cell 151 (1): 68–79. doi:10.1016/j.cell.2012.08.033. PMID 23021216.
^ Kessler JD, Kahle KT, Sun T, Meerbrey KL, Schlabach MR, Schmitt EM, Skinner SO, Xu Q, Li MZ, Hartman ZC, Rao M, Yu P, Dominguez-Vidana R, Liang AC, Solimini NL, Bernardi RJ, Yu B, Hsu T, Golding I, Luo J, Osborne CK, Creighton CJ, Hilsenbeck SG, Schiff R, Shaw CA, Elledge SJ, Westbrook TF (January 2012). "A SUMOylation-dependent transcriptional subprogram is required for Myc-driven tumorigenesis". Science 335 (6066): 348–53. doi:10.1126/science.1212728. PMID 22157079.
^ Ross JS, Ali SM, Wang K, Palmer G, Yelensky R, Lipson D, Miller VA, Zajchowski D, Shawver LK, Stephens PJ (September 2013). "Comprehensive genomic profiling of epithelial ovarian cancer by next generation sequencing-based diagnostic assay reveals new routes to targeted therapies". Gynecol. Oncol. 130 (3): 554–9. doi:10.1016/j.ygyno.2013.06.019. PMID 23791828.
^ Chen Y, McGee J, Chen X, Doman TN, Gong X, Zhang Y, Hamm N, Ma X, Higgs RE, Bhagwat SV, Buchanan S, Peng SB, Staschke KA, Yadav V, Yue Y, Kouros-Mehr H (2014). "Identification of Druggable Cancer Driver Genes Amplified across TCGA Datasets.". PLoS ONE 9 (5): e98293. doi:10.1371/journal.pone.0098293. PMC 4038530. PMID 24874471.
^ Land H, Parada LF, Weinberg RA (1983). "Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes.". Nature. 304 (5927): 596–602. doi:10.1038/304596a0. PMID 6308472.
^ Radner H, el-Shabrawi Y, Eibl RH, Brüstle O, Kenner L, Kleihues P, Wiestler OD (1993). "Tumor induction by ras and myc oncogenes in fetal and neonatal brain: modulating effects of developmental stage and retroviral dose". Acta neuropathologica 86 (5): 456–465. doi:10.1007/bf00228580. PMID 8310796.
^ ^a ^b ^c ^d Park J, Wood MA, Cole MD (2002). "BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation". Mol. Cell. Biol. 22 (5): 1307–16. doi:10.1128/mcb.22.5.1307-1316.2002. PMC 134713. PMID 11839798.
^ ^a ^b Li H, Lee TH, Avraham H (2002). "A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer". J. Biol. Chem. 277 (23): 20965–73. doi:10.1074/jbc.M112231200. PMID 11916966.
^ Xiong J, Fan S, Meng Q, Schramm L, Wang C, Bouzahza B, Zhou J, Zafonte B, Goldberg ID, Haddad BR, Pestell RG, Rosen EM (2003). "BRCA1 inhibition of telomerase activity in cultured cells". Mol. Cell. Biol. 23 (23): 8668–90. doi:10.1128/mcb.23.23.8668-8690.2003. PMC 262673. PMID 14612409.
^ Zhou C, Liu J (2003). "Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells". Biochem. Biophys. Res. Commun. 303 (1): 130–6. doi:10.1016/s0006-291x(03)00318-8. PMID 12646176.
^ Wang Q, Zhang H, Kajino K, Greene MI (1998). "BRCA1 binds c-Myc and inhibits its transcriptional and transforming activity in cells". Oncogene 17 (15): 1939–48. doi:10.1038/sj.onc.1202403. PMID 9788437.
^ ^a ^b Jin Z, Gao F, Flagg T, Deng X (2004). "Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation". J. Biol. Chem. 279 (38): 40209–19. doi:10.1074/jbc.M404056200. PMID 15210690.
^ Kanazawa S, Soucek L, Evan G, Okamoto T, Peterlin BM (2003). "c-Myc recruits P-TEFb for transcription, cellular proliferation and apoptosis". Oncogene 22 (36): 5707–11. doi:10.1038/sj.onc.1206800. PMID 12944920.
^ Brenner C, Deplus R, Didelot C, Loriot A, Viré E, De Smet C, Gutierrez A, Danovi D, Bernard D, Boon T, Pelicci PG, Amati B, Kouzarides T, de Launoit Y, Di Croce L, Fuks F (2005). "Myc represses transcription through recruitment of DNA methyltransferase corepressor". EMBO J. 24 (2): 336–46. doi:10.1038/sj.emboj.7600509. PMC 545804. PMID 15616584.
^ ^a ^b Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM (2001). "The p400 complex is an essential E1A transformation target". Cell 106 (3): 297–307. doi:10.1016/s0092-8674(01)00450-0. PMID 11509179.
^ Roy AL, Carruthers C, Gutjahr T, Roeder RG (1993). "Direct role for Myc in transcription initiation mediated by interactions with TFII-I". Nature 365 (6444): 359–61. doi:10.1038/365359a0. PMID 8377829.
^ Frank SR, Parisi T, Taubert S, Fernandez P, Fuchs M, Chan HM, Livingston DM, Amati B (2003). "MYC recruits the TIP60 histone acetyltransferase complex to chromatin". EMBO Rep. 4 (6): 575–80. doi:10.1038/sj.embor.embor861. PMC 1319201. PMID 12776177.
^ Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, Dang CV, Thomas-Tikhonenko A, Mendell JT (2008). "Widespread microRNA repression by Myc contributes to tumorigenesis". Nat. Genet. 40 (1): 43–50. doi:10.1038/ng.2007.30. PMC 2628762. PMID 18066065.
^ Koscianska E, Baev V, Skreka K, Oikonomaki K, Rusinov V, Tabler M, Kalantidis K (2007). "Prediction and preliminary validation of oncogene regulation by miRNAs". BMC Mol. Biol. 8: 79. doi:10.1186/1471-2199-8-79. PMC 2096627. PMID 17877811.
^ Ioannidis P, Mahaira LG, Perez SA, Gritzapis AD, Sotiropoulou PA, Kavalakis GJ, Antsaklis AI, Baxevanis CN, Papamichail M (2005). "CRD-BP/IMP1 expression characterizes cord blood CD34+ stem cells and affects c-myc and IGF-II expression in MCF-7 cancer cells". J. Biol. Chem. 280 (20): 20086–93. doi:10.1074/jbc.M410036200. PMID 15769738.
^ Gupta S, Davis RJ (1994). "MAP kinase binds to the NH2-terminal activation domain of c-Myc". FEBS Lett. 353 (3): 281–5. doi:10.1016/0014-5793(94)01052-8. PMID 7957875.
^ Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7337–42. doi:10.1073/pnas.94.14.7337. PMC 23822. PMID 9207092.
^ Noguchi K, Kitanaka C, Yamana H, Kokubu A, Mochizuki T, Kuchino Y (1999). "Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase". J. Biol. Chem. 274 (46): 32580–7. doi:10.1074/jbc.274.46.32580. PMID 10551811.
^ ^a ^b 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: 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
^ ^a ^b McMahon SB, Wood MA, Cole MD (2000). "The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc". Mol. Cell. Biol. 20 (2): 556–62. doi:10.1128/mcb.20.2.556-562.2000. PMC 85131. PMID 10611234.
^ ^a ^b McMahon SB, Van Buskirk HA, Dugan KA, Copeland TD, Cole MD (1998). "The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins". Cell 94 (3): 363–74. doi:10.1016/s0092-8674(00)81479-8. PMID 9708738.
^ ^a ^b Cheng SW, Davies KP, Yung E, Beltran RJ, Yu J, Kalpana GV (1999). "c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function". Nat. Genet. 22 (1): 102–5. doi:10.1038/8811. PMID 10319872.
^ ^a ^b Mac Partlin M, Homer E, Robinson H, McCormick CJ, Crouch DH, Durant ST, Matheson EC, Hall AG, Gillespie DA, Brown R (2003). "Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX". Oncogene 22 (6): 819–25. doi:10.1038/sj.onc.1206252. PMID 12584560.
^ Blackwood EM, Eisenman RN (1991). "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc". Science 251 (4998): 1211–7. doi:10.1126/science.2006410. PMID 2006410.
^ Lee CM, Onésime D, Reddy CD, Dhanasekaran N, Reddy EP (2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. 99 (22): 14189–94. doi:10.1073/pnas.232310199. PMC 137859. PMID 12391307.
^ Billin AN, Eilers AL, Queva C, Ayer DE (1999). "Mlx, a novel Max-like BHLHZip protein that interacts with the Max network of transcription factors". J. Biol. Chem. 274 (51): 36344–50. doi:10.1074/jbc.274.51.36344. PMID 10593926.
^ Gupta K, Anand G, Yin X, Grove L, Prochownik EV (1998). "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc". Oncogene 16 (9): 1149–59. doi:10.1038/sj.onc.1201634. PMID 9528857.
^ Meroni G, Reymond A, Alcalay M, Borsani G, Tanigami A, Tonlorenzi R, Lo Nigro C, Messali S, Zollo M, Ledbetter DH, Brent R, Ballabio A, Carrozzo R (1997). "Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor". EMBO J. 16 (10): 2892–906. doi:10.1093/emboj/16.10.2892. PMC 1169897. PMID 9184233.
^ Nair SK, Burley SK (2003). "X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors". Cell 112 (2): 193–205. doi:10.1016/s0092-8674(02)01284-9. PMID 12553908.
^ FitzGerald MJ, Arsura M, Bellas RE, Yang W, Wu M, Chin L, Mann KK, DePinho RA, Sonenshein GE (1999). "Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc". Oncogene 18 (15): 2489–98. doi:10.1038/sj.onc.1202611. PMID 10229200.
^ Meroni G, Cairo S, Merla G, Messali S, Brent R, Ballabio A, Reymond A (2000). "Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway?". Oncogene 19 (29): 3266–77. doi:10.1038/sj.onc.1203634. PMID 10918583.
^ Guo Q, Xie J, Dang CV, Liu ET, Bishop JM (1998). "Identification of a large Myc-binding protein that contains RCC1-like repeats". Proc. Natl. Acad. Sci. U.S.A. 95 (16): 9172–7. doi:10.1073/pnas.95.16.9172. PMC 21311. PMID 9689053.
^ Taira T, Maëda J, Onishi T, Kitaura H, Yoshida S, Kato H, Ikeda M, Tamai K, Iguchi-Ariga SM, Ariga H (1998). "AMY-1, a novel C-MYC binding protein that stimulates transcription activity of C-MYC". Genes Cells 3 (8): 549–65. doi:10.1046/j.1365-2443.1998.00206.x. PMID 9797456.
^ Izumi H, Molander C, Penn LZ, Ishisaki A, Kohno K, Funa K (2001). "Mechanism for the transcriptional repression by c-Myc on PDGF beta-receptor". J. Cell. Sci. 114 (Pt 8): 1533–44. PMID 11282029.
^ Taira T, Sawai M, Ikeda M, Tamai K, Iguchi-Ariga SM, Ariga H (1999). "Cell cycle-dependent switch of up-and down-regulation of human hsp70 gene expression by interaction between c-Myc and CBF/NF-Y". J. Biol. Chem. 274 (34): 24270–9. doi:10.1074/jbc.274.34.24270. PMID 10446203.
^ Uramoto H, Izumi H, Ise T, Tada M, Uchiumi T, Kuwano M, Yasumoto K, Funa K, Kohno K (2002). "p73 Interacts with c-Myc to regulate Y-box-binding protein-1 expression". J. Biol. Chem. 277 (35): 31694–702. doi:10.1074/jbc.M200266200. PMID 12080043.
^ ^a ^b ^c ^d ^e ^f Liu X, Tesfai J, Evrard YA, Dent SY, Martinez E (2003). "c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation". J. Biol. Chem. 278 (22): 20405–12. doi:10.1074/jbc.M211795200. PMID 12660246.
^ Mori K, Maeda Y, Kitaura H, Taira T, Iguchi-Ariga SM, Ariga H (1998). "MM-1, a novel c-Myc-associating protein that represses transcriptional activity of c-Myc". J. Biol. Chem. 273 (45): 29794–800. doi:10.1074/jbc.273.45.29794. PMID 9792694.
^ Fujioka Y, Taira T, Maeda Y, Tanaka S, Nishihara H, Iguchi-Ariga SM, Nagashima K, Ariga H (2001). "MM-1, a c-Myc-binding protein, is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer". J. Biol. Chem. 276 (48): 45137–44. doi:10.1074/jbc.M106127200. PMID 11567024.
^ ^a ^b Feng XH, Liang YY, Liang M, Zhai W, Lin X (2002). "Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B)". Mol. Cell 9 (1): 133–43. doi:10.1016/s1097-2765(01)00430-0. PMID 11804592.
^ Otsuki Y, Tanaka M, Kamo T, Kitanaka C, Kuchino Y, Sugimura H (2003). "Guanine nucleotide exchange factor, Tiam1, directly binds to c-Myc and interferes with c-Myc-mediated apoptosis in rat-1 fibroblasts". J. Biol. Chem. 278 (7): 5132–40. doi:10.1074/jbc.M206733200. PMID 12446731.
^ Gaubatz S, Imhof A, Dosch R, Werner O, Mitchell P, Buettner R, Eilers M (1995). "Transcriptional activation by Myc is under negative control by the transcription factor AP-2". EMBO J. 14 (7): 1508–19. PMC 398238. PMID 7729426.
^ Shrivastava A, Saleque S, Kalpana GV, Artandi S, Goff SP, Calame K (1993). "Inhibition of transcriptional regulator Yin-Yang-1 by association with c-Myc". Science 262 (5141): 1889–92. doi:10.1126/science.8266081. PMID 8266081.
^ Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, Möröy T, Bartek J, Massagué J, Hänel F, Eilers M (2001). "Repression of p15INK4b expression by Myc through association with Miz-1". Nat. Cell Biol. 3 (4): 392–9. doi:10.1038/35070076. PMID 11283613.
^ Peukert K, Staller P, Schneider A, Carmichael G, Hänel F, Eilers M (1997). "An alternative pathway for gene regulation by Myc". EMBO J. 16 (18): 5672–86. doi:10.1093/emboj/16.18.5672. PMC 1170199. PMID 9312026.

External links

The Myc Protein
NCBI Human Myc protein
Myc cancer gene
myc Proto-Oncogene Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)
Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4
Drosophila Myc - The Interactive Fly
FactorBook C-Myc

UpToDate Contents

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1. バーキットリンパ腫の病理学 pathobiology of burkitt lymphoma
2. びまん性大細胞型B細胞性リンパ腫および原発性縦隔大細胞型B細胞リンパ腫の病理学 pathobiology of diffuse large b cell lymphoma and primary mediastinal large b cell lymphoma
3. びまん性大細胞型B細胞性リンパ腫の予後 prognosis of diffuse large b cell lymphoma
4. バーキットリンパ腫の疫学、臨床症状、病理学的特徴、および診断 epidemiology clinical manifestations pathologic features and diagnosis of burkitt lymphoma
5. 頭頸部の扁平上皮癌化：分子学的および遺伝学的変化 head and neck squamous cell carcinogenesis molecular and genetic alterations

English Journal

Combinational delivery of c-myc siRNA and nucleoside analogs in a single, synthetic nanocarrier for targeted cancer therapy.

Zhang Y, Peng L, Mumper RJ, Huang L.SourceDivision of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Biomaterials.Biomaterials.2013 Nov;34(33):8459-68. doi: 10.1016/j.biomaterials.2013.07.050. Epub 2013 Aug 8.
The treatment of aggressive non-small-cell lung cancer (NSCLC) depends on the creation of new therapeutic regimens in clinical settings. In this study, we developed a Lipid/Calcium/Phosphate (LCP) nanoparticle that combines chemotherapy with gene therapy. By encapsulating a chemodrug, gemcitabine mo
PMID 23932296

1,1-Bis (3'-indolyl)-1-(p-substitutedphenyl)methane compounds inhibit lung cancer cell and tumor growth in a metastasis model.

Andey T, Patel A, Jackson T, Safe S, Singh M.SourceDepartment of Pharmaceutics, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 1520 South Martin Luther King Jr. Blvd., Tallahassee, FL 32307, USA.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2013 Oct 9;50(2):227-41. doi: 10.1016/j.ejps.2013.07.007. Epub 2013 Jul 23.
1,1-Bis(3-indolyl)-1-(p-substitutedphenyl)methane (C-DIM) compounds exhibit remarkable antitumor activity with low toxicity in various cancer cells including lung tumors. Two C-DIM analogs, DIM-C-pPhOCH3 (C-DIM-5) and DIM-C-pPhOH (C-DIM-8) while acting differentially on the orphan nuclear receptor,
PMID 23892137

Mechanistic studies for the role of cellular nucleic-acid-binding protein (CNBP) in regulation of c-myc transcription.

Chen S, Su L, Qiu J, Xiao N, Lin J, Tan JH, Ou TM, Gu LQ, Huang ZS, Li D.SourceSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China.
Biochimica et biophysica acta.Biochim Biophys Acta.2013 Oct;1830(10):4769-77. doi: 10.1016/j.bbagen.2013.06.007. Epub 2013 Jun 14.
BACKGROUND: Guanine-rich sequence of c-myc nuclease hypersensitive element (NHE) III1 is known to fold in G-quadruplex and subsequently serves as a transcriptional silencer. Cellular nucleic-acid-binding protein (CNBP), a highly conserved zinc-finger protein with multiple biological functions, could
PMID 23774591

Japanese Journal

Induced pluripotent stem cells: opportunities and challenges.

Okita Keisuke,Yamanaka Shinya
Philosophical transactions of the Royal Society of London. Series B, Biological sciences 366, 2183-2197, 2011-08-12
… Somatic cells have been reprogrammed into pluripotent stem cells by introducing a combination of several transcription factors, such as Oct3/4, Sox2, Klf4 and c-Myc. …
NAID 120003255724

当科におけるバーキットリンパ腫/白血病治療成績の向上

笹崎美幸,森政樹,上澤光世,藤原慎一郎,菊池裕二,佐藤一也,松山智洋,大嶺謙,上田真寿,鈴木隆浩,尾崎勝俊,永井正,室井一男,小澤敬也
自治医科大学紀要 33, 23-28, 2011-03-01
… バーキットリンパ腫/白血病(Burkitt lymphoma/leukemia;BL)はc-myc遺伝子(8q24)と免疫グロブリン(Ig)遺伝子の相互転座に起因する高悪性度B細胞腫瘍であり,急速に進行する病態を特徴とする。 …
NAID 110008506938

Related Pictures

がん原因遺伝子の働きなしで HIF-a subunitとc-Myc Myc and Apoptosis raf signaling induced c myc activation the figure 6 proposed model for c myc Pathways involving c-MYC and apoptosis CHIP and c-Myc Figure 1.

★リンクテーブル★

リンク元	「バーキットリンパ腫」
拡張検索	「癌原遺伝子産物c-Myc」「c-Myc protein」「c-Mycタンパク質」「proto-oncogene protein c-Myc」
関連記事	「C」「M」「c」

「バーキットリンパ腫」

V-myc avian myelocytomatosis viral oncogene homolog
	; Structure of the c-Myc (red) in complex with Max (blue) and DNA (PDB 1nkp). Both proteins are binding the major groove of the DNA by forming a fork-like structure.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1A93, 1EE4, 1MV0, 1NKP, 2A93, 2OR9
Identifiers
Symbols	MYC ; MRTL; MYCC; bHLHe39; c-Myc
External IDs	OMIM: 190080 MGI: 97250 HomoloGene: 31092 ChEMBL: 1250348 GeneCards: MYC Gene
Gene ontology
Molecular function	• RNA polymerase II core promoter proximal region sequence-specific DNA binding; • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; • DNA binding; • sequence-specific DNA binding transcription factor activity; • protein binding; • transcription factor binding; • protein complex binding; • protein dimerization activity; • repressing transcription factor binding; • E-box binding;
Cellular component	• nucleus; • nucleoplasm; • nucleolus; • spindle; • protein complex;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • MAPK cascade; • branching involved in ureteric bud morphogenesis; • positive regulation of mesenchymal cell proliferation; • energy reserve metabolic process; • chromatin remodeling; • transcription, DNA-templated; • transcription initiation from RNA polymerase II promoter; • cellular iron ion homeostasis; • cellular response to DNA damage stimulus; • cell cycle arrest; • transforming growth factor beta receptor signaling pathway; • Notch signaling pathway; • positive regulation of cell proliferation; • response to gamma radiation; • gene expression; • regulation of gene expression; • oxygen transport; • regulation of telomere maintenance; • negative regulation of stress-activated MAPK cascade; • cellular response to UV; • cellular response to drug; • response to drug; • negative regulation of apoptotic process; • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; • fibroblast apoptotic process; • negative regulation of monocyte differentiation; • positive regulation of transcription, DNA-templated; • positive regulation of transcription from RNA polymerase II promoter; • positive regulation of fibroblast proliferation; • negative regulation of fibroblast proliferation; • positive regulation of epithelial cell proliferation; • chromosome organization; • negative regulation of cell division; • canonical Wnt signaling pathway; • response to growth factor; • positive regulation of metanephric cap mesenchymal cell proliferation; • positive regulation of DNA biosynthetic process; • positive regulation of response to DNA damage stimulus;
	Sources: Amigo / QuickGO
Orthologs
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