MYB (gene) explained

Myb genes are part of a large gene family of transcription factors found in animals and plants. In humans, it includes Myb proto-oncogene like 1 and Myb-related protein B in addition to MYB proper.^{[1] [2]} Members of the extended SANT/Myb family also include the SANT domain and other similar all-helical homeobox-like domains.

Function

Viral

The Myb gene family is named after the eponymous gene in Avian myeloblastosis virus. The viral Myb (v-Myb,) recognizes the sequence 5'-YAACKG-3'. It causes myeloblastosis (myeloid leukemia) in chickens.^[3] Compared to the normal animal cellular Myb (c-myb), v-myb contains deletions in the C-terminal regulatory domain, leading to aberrant activation of other oncogenes.^[4]

Animals

Myb proto-oncogene protein is a member of the MYB (myeloblastosis) family of transcription factors. The protein contains three domains, an N-terminal DNA-binding domain, a central transcriptional activation domain and a C-terminal domain involved in transcriptional repression. It may play a role in cell cycle regulation. Like the viral version, this gene is an oncogene, and rearrangements of the gene (often involving deletion in the C-terminal domain) causes cancer.^[4]

Plants

MYB factors represent a family of proteins that include the conserved MYB DNA-binding domain. Plants contain a MYB-protein subfamily that is characterised by the R2R3-type MYB domain.^[5]

In maize, phlobaphenes are synthesized in the flavonoids synthetic pathway^[6] from polymerisation of flavan-4-ols^{[7] [8]} which encodes an R2R3 myb-like transcriptional activator^[9] of the A1 gene encoding for the dihydroflavonol 4-reductase (reducing dihydroflavonols into flavan-4-ols)^[10] while another gene (Suppressor of Pericarp Pigmentation 1 or SPP1) acts as a suppressor.^[11] The maize P gene encodes a Myb homolog that recognizes the sequence CCWACC, in sharp contrast with the YAACGG bound by vertebrate Myb proteins.^[12]

In sorghum, the corresponding yellow seed 1 gene (y1)^[13] also encodes a R2R3 type of Myb domain protein that regulates the expression of chalcone synthase, chalcone isomerase and dihydroflavonol reductase genes required for the biosynthesis of 3-deoxyflavonoids.^[14]

Ruby is a MYB transcriptional activator of genes that produce anthocyanin in citrus fruits. In most citrus varieties Ruby is non-functional, but in blood oranges it upregulates anthocyanin production to produce the characteristic red color of the fruit.^[15]

See also

• EZH1

Further reading

• Oh IH, Reddy EP . The myb gene family in cell growth, differentiation and apoptosis. . Oncogene . 18 . 19 . 3017–33 . 1999 . 10378697 . 10.1038/sj.onc.1202839 . free .
• Nicolaides NC, Gualdi R, Casadevall C, Manzella L, Calabretta B . Positive autoregulation of c-myb expression via Myb binding sites in the 5' flanking region of the human c-myb gene. . Mol. Cell. Biol. . 11 . 12 . 6166–76 . 1991 . 1944282 . 361795 . 10.1128/mcb.11.12.6166-6176.1991.
• Kalkbrenner F, Guehmann S, Moelling K . Transcriptional activation by human c-myb and v-myb genes. . Oncogene . 5 . 5 . 657–61 . 1990 . 2189102 .
• Westin EH, Gorse KM, Clarke MF . Alternative splicing of the human c-myb gene. . Oncogene . 5 . 8 . 1117–24 . 1990 . 2202948 .
• Dasgupta P, Reddy EP . Identification of alternatively spliced transcripts for human c-myb: molecular cloning and sequence analysis of human c-myb exon 9A sequences. . Oncogene . 4 . 12 . 1419–23 . 1990 . 2687764 .
• Janssen JW, Vernole P, de Boer PA, Oosterhuis JW, Collard JG . Sublocalization of c-myb to 6q21----q23 by in situ hybridization and c-myb expression in a human teratocarcinoma with 6q rearrangements. . Cytogenet. Cell Genet. . 41 . 3 . 129–35 . 1986 . 3007038 . 10.1159/000132217 .
• Slamon DJ, Boone TC, Murdock DC, Keith DE, Press MF, Larson RA, Souza LM . Studies of the human c-myb gene and its product in human acute leukemias. . Science . 233 . 4761 . 347–51 . 1986 . 3014652 . 10.1126/science.3014652 . 1986Sci...233..347S .
• Majello B, Kenyon LC, Dalla-Favera R . Human c-myb protooncogene: nucleotide sequence of cDNA and organization of the genomic locus. . Proc. Natl. Acad. Sci. U.S.A. . 83 . 24 . 9636–40 . 1987 . 3540945 . 387195 . 10.1073/pnas.83.24.9636 . free .
• Szczylik C, Skorski T, Ku DH, Nicolaides NC, Wen SC, Rudnicka L, Bonati A, Malaguarnera L, Calabretta B . Regulation of proliferation and cytokine expression of bone marrow fibroblasts: role of c-myb. . J. Exp. Med. . 178 . 3 . 997–1005 . 1993 . 7688794 . 2191153 . 10.1084/jem.178.3.997 .
• Krieg J, Oelgeschläger M, Janknecht R, Lüscher B . High affinity DNA binding of native full length c-Myb and differential proteolytic sensitivity of its N- and C-terminal domains. . Oncogene . 10 . 11 . 2221–8 . 1995 . 7784067 .
• Jacobs SM, Gorse KM, Westin EH . Identification of a second promoter in the human c-myb proto-oncogene. . Oncogene . 9 . 1 . 227–35 . 1994 . 8302584 .
• Favier D, Gonda TJ . Detection of proteins that bind to the leucine zipper motif of c-Myb. . Oncogene . 9 . 1 . 305–11 . 1994 . 8302594 .
• Glaser R, Lafuse WP, Bonneau RH, Atkinson C, Kiecolt-Glaser JK . Stress-associated modulation of proto-oncogene expression in human peripheral blood leukocytes. . Behav. Neurosci. . 107 . 3 . 525–9 . 1993 . 8329139 . 10.1037/0735-7044.107.3.525 .
• Dash AB, Orrico FC, Ness SA . The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb. . Genes Dev. . 10 . 15 . 1858–69 . 1996 . 8756344 . 10.1101/gad.10.15.1858 . free .
• Vorbrueggen G, Lovrić J, Moelling K . Functional analysis of phosphorylation at serine 532 of human c-Myb by MAP kinase. . Biol. Chem. . 377 . 11 . 721–30 . 1997 . 8960373 . 10.1515/bchm3.1996.377.11.721 .
• Tavner FJ, Simpson R, Tashiro S, Favier D, Jenkins NA, Gilbert DJ, Copeland NG, Macmillan EM, Lutwyche J, Keough RA, Ishii S, Gonda TJ . Molecular cloning reveals that the p160 Myb-binding protein is a novel, predominantly nucleolar protein which may play a role in transactivation by Myb. . Mol. Cell. Biol. . 18 . 2 . 989–1002 . 1998 . 9447996 . 108811 . 10.1128/MCB.18.2.989.
• Hedge SP, Kumar A, Kurschner C, Shapiro LH . c-Maf interacts with c-Myb to regulate transcription of an early myeloid gene during differentiation. . Mol. Cell. Biol. . 18 . 5 . 2729–37 . 1998 . 9566892 . 110652 . 10.1128/mcb.18.5.2729.
• Leverson JD, Koskinen PJ, Orrico FC, Rainio EM, Jalkanen KJ, Dash AB, Eisenman RN, Ness SA . Pim-1 kinase and p100 cooperate to enhance c-Myb activity. . Mol. Cell . 2 . 4 . 417–25 . 1998 . 9809063 . 10.1016/S1097-2765(00)80141-0 . free .
• Thompson MA, Rosenthal MA, Ellis SL, Friend AJ, Zorbas MI, Whitehead RH, Ramsay RG . c-Myb down-regulation is associated with human colon cell differentiation, apoptosis, and decreased Bcl-2 expression. . Cancer Res. . 58 . 22 . 5168–75 . 1998 . 9823328 .
• Verbeek W, Gombart AF, Chumakov AM, Müller C, Friedman AD, Koeffler HP . C/EBPepsilon directly interacts with the DNA binding domain of c-myb and cooperatively activates transcription of myeloid promoters. . Blood . 93 . 10 . 3327–37 . 1999 . 10233885 . 10.1182/blood.V93.10.3327. free .

External links

• • Drosophila Myb oncogene-like - The Interactive Fly
• Arabidospsis thaliana MYB family at Database of Arabidopsis Transcription Factors (DATF)

Notes and References

1. Chen Y, Xu H, Liu J, Zhang C, Leutz A, Mo X . The c-Myb functions as a downstream target of PDGF-mediated survival signal in vascular smooth muscle cells . Biochem Biophys Res Commun . 360 . 2 . 433–6 . Jul 2007 . 17599807 . 10.1016/j.bbrc.2007.06.078 .
2. Web site: Entrez Gene: v-myb myeloblastosis viral oncogene homolog (avian).
3. Klempnauer KH, Symonds G, Evan GI, Bishop JM . Subcellular localization of proteins encoded by oncogenes of avian myeloblastosis virus and avian leukemia virus E26 and by chicken c-myb gene . Cell . 37 . 2 . 537–47 . June 1984 . 6327074 . 10.1016/0092-8674(84)90384-2. 46196167 .
4. George OL, Ness SA . Situational awareness: regulation of the myb transcription factor in differentiation, the cell cycle and oncogenesis . Cancers . 6 . 4 . 2049–71 . October 2014 . 25279451 . 10.3390/cancers6042049 . 4276956 . free .
5. Stracke R, Werber M, Weisshaar B . The R2R3-MYB gene family in Arabidopsis thaliana . Curr. Opin. Plant Biol. . 4 . 5 . 447–56 . October 2001 . 11597504 . 10.1016/s1369-5266(00)00199-0 . 2001COPB....4..447S .
6. Himi E, Mares DJ, Yanagisawa A, Noda K . Effect of grain colour gene (R) on grain dormancy and sensitivity of the embryo to abscisic acid (ABA) in wheat . J. Exp. Bot. . 53 . 374 . 1569–74 . July 2002 . 12096095 . 10.1093/jxb/erf005 . free .
7. Winkel-Shirley B . Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology . Plant Physiol. . 126 . 2 . 485–93 . June 2001 . 11402179 . 1540115 . 10.1104/pp.126.2.485 .
8. Chopra S, Cocciolone SM, Bushman S, Sangar V, McMullen MD, Peterson T . The maize unstable factor for orange1 is a dominant epigenetic modifier of a tissue specifically silent allele of pericarp color1 . Genetics . 163 . 3 . 1135–46 . March 2003 . 10.1093/genetics/163.3.1135 . 12663550 . 1462483 .
9. http://www.intl-pag.org/16/abstracts/PAG16_P05d_343.html Structural And Transcriptional Analysis Of The Complex P1-wr Cluster In Maize. Wolfgang Goettel, Joachim Messing. Plant & Animal Genomes XVI Conference
10. Dong X, Braun EL, Grotewold E . Functional conservation of plant secondary metabolic enzymes revealed by complementation of Arabidopsis flavonoid mutants with maize genes . Plant Physiol. . 127 . 1 . 46–57 . September 2001 . 11553733 . 117961 . 10.1104/pp.127.1.46 . 1811/48809 .
11. Suppressor of Pericarp Pigmentation 1 (SPP1), a novel gene involved in phlobaphene accumulation in maize (Zea mays L.) pericarps. . Lee EA, Harper V . Maydica . 2002 . 47 . 1 . 51–58 .
12. Grotewold E, Drummond BJ, Bowen B, Peterson T . 1994. The myb-homologous P gene controls phlobaphene pigmentation in maize floral organs by directly activating a flavonoid biosynthetic gene subset . Cell . 76 . 3. 543–554 . 10.1016/0092-8674(94)90117-1 . 8313474 . 42197232.
13. Characterization of a deletion allele of a sorghum Myb gene yellow seedl showing loss of 3-deoxyflavonoids . Boddu J, Svabek C, Ibraheem F, Jones AD, Chopra S . Plant Science . 2005 . 169 . 3 . 542–552 . 10.1016/j.plantsci.2005.05.007.
14. Boddu J, Jiang C, Sangar V, Olson T, Peterson T, Chopra S . Comparative structural and functional characterization of sorghum and maize duplications containing orthologous myb transcription regulators of 3-deoxyflavonoid biosynthesis . Plant Mol. Biol. . 60 . 2 . 185–99 . January 2006 . 16429259 . 10.1007/s11103-005-3568-1 . 23841582 .
15. Butelli E, Licciardello C, Zhang Y, Liu J, Mackay S, Bailey P, Reforgiato-Recupero G, Martin C . Retrotransposons control fruit-specific, cold-dependent accumulation of anthocyanins in blood oranges . Plant Cell . 24 . 3 . 1242–55 . 2012 . 22427337 . 3336134 . 10.1105/tpc.111.095232 .