Myc

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V-myc mielocitomatozni viralni onkogenski homolog

Struktura c-Myc (crveno) u kompleksu sa Max (plavo) i DNK (1nkp). Oba proteina su vezana za veliki žleb DNK čime formiraju strukturu sličnu račvi.

Dostupne strukture

1A93, 1EE4, 1MV0, 1NKP, 2A93

Identifikatori

Simboli

MYC; MRTL; bHLHe39; c-Myc

Vanjski ID

OMIM: 190080 MGI: 97250 HomoloGene: 31092 GeneCards: MYC Gene

Ontologija gena
Molekularna funkcija	• DNK vezivanje • Aktivnost transkripcionog faktora specifičnog za specifičnu DNA sekvencu • proteinsko vezivanje • vezivanje transkripcionog faktora • vezivanje proteinskog kompleksa • vezivanje represivnog transkripcionog faktora • vezivanje E-kutije
Celularna komponenta	• nukleus • nukleoplazma • nukleolus • vreteno • proteinski kompleks
Biološki proces	• negativna regulacija transkripcije putem promotera RNK polimeraze II • MAPK kaskada • razgranavanje koje učestvuje u morfogenezi ureterinskog zametka • pozitivna regulacija mezenhimalne ćelijske proliferacije • metabolički proces energijske rezerve • remodelovanje hromatina

Ortolozi

Vrsta

Čovek

Miš

Entrez

4609

17869

Ensembl

ENSG00000136997

ENSMUSG00000022346

UniProt

P01106

P01108

RefSeq (mRNA)

NM_002467.4

NM_001177352.1

RefSeq (protein)

NP_002458.2

NP_001170823.1

Lokacija (UCSC)

Chr 8:
128.75 - 128.75 Mb

Chr 15:
61.82 - 61.82 Mb

PubMed pretraga

[1]

[2]

Myc (c-Myc) je regulatorni gen koji kodira transkripcioni faktor.

Mutirane verzije Myc gena su nađene u mnoštvu tipova kancera. One uzrokuju konstitutivnu (perzistentnu) ekspresiju gena. To dovodi do umanjenog izražavanja mnoštva gena, neki od kojih učestvuju u ćelijskoj proliferaciji, i time se formira kancer. Česta translokacija koja obuhvata Myc je t(8;14). Ona je kritična za razvoj u mnogim slučajevima Burkitovog limfoma. Nedavna istraživanja demonstriraju da privremena inhibicija Myc faktora selektivno ubija ćelije kancera pluća kod miševa, te je stoga ovaj protein potencijalni cilj za lekove protiv kancera.^[1]

U humanom genomu, Myc je lociran na hromozomu 8 i smatra se da reguliše izražavanje 15% svih gena^[2] putem vezivanja za sekvencu pojačivačke kutije (E-kutija) i regrutovanja histonske acetiltransferaze (HAT). To znači da osim njegove uloge klasičnog transkripcionog faktora, Myc takođe deluje kao globalni regulator hromatinske strukture putem regulacije histonske acetilacije u regionima bogatim genima, kao i na mestima udaljenim od poznatih gena.^[3]

Reference

↑ Soucek L, Whitfield J, Martins CP, Finch AJ, Murphy DJ, Sodir NM, Karnezis AN, Swigart LB, Nasi S, Evan GI (October 2008). „Modelling Myc inhibition as a cancer therapy”. Nature 455 (7213): 679–83. DOI:10.1038/nature07260. PMID 18716624.
↑ Gearhart J, Pashos EE, Prasad MK, Pluripotency Redeux -- advances in stem-cell research, N Engl J Med 357(15):1469 Free full text Arhivirano 2008-10-19 na Wayback Machine-u
↑ 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.

Literatura

Ruf IK, Rhyne PW, Yang H, et al. (2002). „EBV regulates c-MYC, apoptosis, and tumorigenicity in Burkitt's lymphoma”. Curr. Top. Microbiol. Immunol. 258: 153–60. PMID 11443860.
Lüscher B (2001). „Function and regulation of the transcription factors of the Myc/Max/Mad network”. Gene 277 (1–2): 1–14. DOI:10.1016/S0378-1119(01)00697-7. PMID 11602341.
Hoffman B, Amanullah A, Shafarenko M, Liebermann DA (2002). „The proto-oncogene c-myc in hematopoietic development and leukemogenesis”. Oncogene 21 (21): 3414–21. DOI:10.1038/sj.onc.1205400. PMID 12032779.
Pelengaris S, Khan M, Evan G (2002). „c-MYC: more than just a matter of life and death”. Nat. Rev. Cancer 2 (10): 764–76. DOI:10.1038/nrc904. PMID 12360279.
Nilsson JA, Cleveland JL (2004). „Myc pathways provoking cell suicide and cancer”. Oncogene 22 (56): 9007–21. DOI:10.1038/sj.onc.1207261. PMID 14663479.
Dang CV, O'donnell KA, Juopperi T (2005). „The great MYC escape in tumorigenesis”. Cancer Cell 8 (3): 177–8. DOI:10.1016/j.ccr.2005.08.005. PMID 16169462.
Dang CV, Li F, Lee LA (2007). „Could MYC induction of mitochondrial biogenesis be linked to ROS production and genomic instability?”. Cell Cycle 4 (11): 1465–6. DOI:10.4161/cc.4.11.2121. PMID 16205115.
Coller HA, Forman JJ, Legesse-Miller A (2007). „"Myc'ed Messages": Myc Induces Transcription of E2F1 while Inhibiting Its Translation via a microRNA Polycistron”. PLoS Genet. 3 (8): e146. DOI:10.1371/journal.pgen.0030146. PMC 1959363. PMID 17784791.
Astrin SM, Laurence J (1992). „Human immunodeficiency virus activates c-myc and Epstein-Barr virus in human B lymphocytes”. Ann. N. Y. Acad. Sci. 651: 422–32. DOI:10.1111/j.1749-6632.1992.tb24642.x. PMID 1318011.
Bernstein PL, Herrick DJ, Prokipcak RD, Ross J (1992). „Control of c-myc mRNA half-life in vitro by a protein capable of binding to a coding region stability determinant”. Genes Dev. 6 (4): 642–54. DOI:10.1101/gad.6.4.642. PMID 1559612.
Iijima S, Teraoka H, Date T, Tsukada K (1992). „DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc oncoprotein”. Eur. J. Biochem. 206 (2): 595–603. DOI:10.1111/j.1432-1033.1992.tb16964.x. PMID 1597196.
Seth A, Alvarez E, Gupta S, Davis RJ (1992). „A phosphorylation site located in the NH2-terminal domain of c-Myc increases transactivation of gene expression”. J. Biol. Chem. 266 (35): 23521–4. PMID 1748630.
Takahashi E, Hori T, O'Connell P, et al. (1991). „Mapping of the MYC gene to band 8q24.12----q24.13 by R-banding and distal to fra(8)(q24.11), FRA8E, by fluorescence in situ hybridization”. Cytogenet. Cell Genet. 57 (2–3): 109–11. DOI:10.1159/000133124. PMID 1914517.
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.
Gazin C, Rigolet M, Briand JP, et al. (1986). „Immunochemical detection of proteins related to the human c-myc exon 1”. EMBO J. 5 (9): 2241–50. PMC 1167107. PMID 2430795.
Lüscher B, Kuenzel EA, Krebs EG, Eisenman RN (1989). „Myc oncoproteins are phosphorylated by casein kinase II”. EMBO J. 8 (4): 1111–9. PMC 400922. PMID 2663470.
Finver SN, Nishikura K, Finger LR, et al. (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”. Proc. Natl. Acad. Sci. U.S.A. 85 (9): 3052–6. DOI:10.1073/pnas.85.9.3052. PMC 280141. PMID 2834731.
Showe LC, Moore RC, Erikson J, Croce CM (1987). „MYC oncogene involved in a t(8;22) chromosome translocation is not altered in its putative regulatory regions”. Proc. Natl. Acad. Sci. U.S.A. 84 (9): 2824–8. DOI:10.1073/pnas.84.9.2824. PMC 304752. PMID 3033665.
Guilhot S, Petridou B, Syed-Hussain S, Galibert F (1989). „Nucleotide sequence 3' to the human c-myc oncogene; presence of a long inverted repeat”. Gene 72 (1–2): 105–8. DOI:10.1016/0378-1119(88)90131-X. PMID 3243428.
Hann SR, King MW, Bentley DL, et al. (1988). „A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas”. Cell 52 (2): 185–95. DOI:10.1016/0092-8674(88)90507-7. PMID 3277717.

Spoljašnje veze

Myc protein
Ljudski Myc protein

PDB Galerija

1nkp: Kristalna struktura Myc-Max prepoznavanja DNK

Transkripcioni faktori i intracelularni receptori

(1) Osnovni domeni

(1.1) Osnovni leucin rajsferšlus (bZIP)	Aktivirajući transkripcioni faktor (AATF, 1, 2, 3, 4, 5, 6, 7) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • BATF • BLZF1 • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3, L1) • CREM • DBP • DDIT3 • GABPA • HLF • MAF (B, F, G, K) • NFE (2, L1, L2) • NFIL3 • NRL • NRF1 • XBP1
(1.2) Osnovni heliks-petlja-heliks (bHLH)	ATOH1 • AhR • AHRR • ARNT • ASCL1 • BHLHB2 • BMAL (ARNTL, ARNTL2) • CLOCK • EPAS1 • HAND (1, 2) • HES (5, 6) • HEY (1, 2, L) • HES1 • HIF (1A, 3A) • ID (1, 2, 3, 4) • LYL1 • MXD4 • MYCL1 • MYCN • Myogenic regulatorni faktori (MyoD, Myogenin, MYF5, MYF6) • Neurogenini (1, 2, 3) • NeuroD (1, 2) • NPAS (1, 2, 3) • OLIG (1, 2) • Pho4 • Scleraxis • TAL (1, 2) • Twist • USF1
(1.3) bHLH-ZIP	AP-4 • MAX • MITF • MNT • MLX • MXI1 • Myc • SREBP (1, 2)
(1.4) NF-1	NFI (A, B, C, X) • SMAD (R-SMAD (1, 2, 3, 5, 9) - I-SMAD (6, 7) - 4)
(1.5) RF-X	RFX (1, 2, 3, 4, 5, ANK)
(1.6) Osnovni heliks-razmak-heliks (bHSH)	AP-2 (α, β, γ, δ, ε)

(2) Cink prst DNA-vezujući domeni

(2.1) Nuklearni receptor (Cys₄)	podfamilija 1 (Tiroidni hormon (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) podfamilija 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testikularni receptor (2, 4), TLX) podfamilija 3 (Steroidni hormon (Androgen, Estrogen (α, β), Glukokortikoid, Mineralokortikoid, Progesteron), Estrogen-vezani (α, β, γ)) podfamilija 4 NUR (NGFIB, NOR1, NURR1) • podfamilija 5 (LRH-1, SF1) • podfamilija 6 (GCNF) • podfamilija 0 (DAX1, SHP)
(2.2) Drugi Cys₄	GATA (1, 2, 3, 4, 5, 6) • MTA (1, 2, 3) • TRPS1
(2.3) Cys₂His₂	Generalni transkripcioni faktori (TFIIA, TFIIB, TFIID, TFIIE, TFIIF (1, 2), TFIIH (1, 2, 4, 2I, 3A, 3C1, 3C2)) ATBF1 • BCL (6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • GFI1 • GLI-Kruppel familija (1, 2, 3, REST, S2, YY1) • HIC (1, 2) • HIVEP (1, 2, 3) • IKZF (1, 2, 3) • ILF (2, 3) • KLF (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 17) • MTF1 • MYT1 • OSR1 • SP (1, 2, 4, 7) • WT1 • Zbtb7 (7A, 7B) • ZBTB (16, 17, 20, 32, 33, 40) • cink prst (3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 318, 330, 346, 350, 365, 366, 384, 423, 451, 452, 471, 593, 638, 649, 655)
(2.4) Cys₆	HIVEP1
(2.5) Naizmenična kompozicija	AIRE • DIDO1 • GRLF1 • ING (1, 2, 4) • JARID (1A, 1B, 1C, 1D, 2) • JMJD1B

(3) Heliks-zavoj-heliks domeni

(3.1) Homeodomen	ARX • CDX (1, 2) • CRX • CUTL1 • DBX (1, 2) • DLX (3, 4, 5) • EMX2 • EN (1, 2) • FHL (1, 2, 3) • HESX1 • HHEX • HLX • Homeobox (A1, A2, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) • HOPX • IRX (1, 2, 3, 4, 5, 6, MKX) • LMX (1A, 1B) • MEIS (1, 2) • MEOX2 • MNX1 • MSX (1, 2) • NANOG • NKX (2-1, 2-2, 2-3, 2-5, 3-1, 3-2, 6-1, 6-2) • PBX (1, 2, 3) • PHF (1, 3, 6, 8, 10, 16, 17, 20, 21A) • PITX (1, 2, 3) • POU domen (PIT-1, BRN-3: A, B, C, Oktamer transkripcioni faktor: 1, 2, 3/4, 6, 7, 11) • OTX (1, 2) • PDX1 • ZEB (1, 2)
(3.2) Paired box	PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
(3.3) Fork glava / winged heliks	E2F (1, 2, 3, 4, 5) • FOX proteini (C1, C2, D3, E1, G1, H1, K2, L2, M1, N3, O1, O3, O4, P1, P2, P3)
(3.4) Faktori toplotnog šoka	HSF (1, 2, 4)
(3.5) Triptofan klasteri	ELF (2, 4, 5) • EGF • ELK (1, 3, 4) • ERF • ERG • ETS (1, 2, SPIB) • ETV (1, 4, 5, 6) • FLI1 • Interferon regulatorni faktori (1, 2, 3, 4, 5, 6, 7, 8) • MYB • MYBL2
(3.6) TEA domen	transkripcioni pojačivač faktor (1, 2, 3, 4)

(4) β-Scaffold faktori sa manjim žljebnim kontaktima

(4.1) Rel homologni region	NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (C1, C2, C3, C4, 5)
(4.2) STAT	STAT (1, 2, 3, 4, 5, 6)
(4.3) p53	p53 • TBX (1, 2, 3, 5, 19, 21, 22, Brahiuri, TBR1)
(4.4) MADS kutija	Mef2 (A, B, C, D) • SRF
(4.6) TATA vezujući proteini	TBP • TBPL1
(4.7) Grupa visoke pokretljivosti	HMGB (1, 2, 3) • HNF (1A, 1B) • LEF1 • SOX (1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 18, 21) • SRY • SSRP1 • TCF (3, 4) • TOX (1, 2, 3, 4)
(4.10) Domen hladnog šoka	CSDA, YBX1
(4.11) Runt	CBF (CBFA2T2, CBFA2T3, RUNX1, RUNX2, RUNX3, RUNX1T1)

(0) Drugi transkripcioni faktori

(0.2) HMGI(Y)	HMGA (1, 2) • HBP1
(0.3) Džep domen	Rb • RBL1 • RBL2
(0.5) AP-2/EREBP-vezani faktori	Apetala 2 • EREBP • B3
(0.6) Razno	ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFY (A, B, C) • Ro/Sigma