title: Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex.
abstract: Members of the Myb oncoprotein and E2F-Rb tumor suppressor protein families are present within the same highly conserved multiprotein transcriptional repressor complex, named either as Myb and synthetic multivuval class B (Myb-MuvB) or as Drosophila Rb E2F and Myb-interacting proteins (dREAM). We now report that the animal-specific C terminus of Drosophila Myb but not the more highly conserved N-terminal DNA-binding domain is necessary and sufficient for (i) adult viability, (ii) proper localization to chromosomes in vivo, (iii) regulation of gene expression in vivo, and (iv) interaction with the highly conserved core of the MuvB/dREAM transcriptional repressor complex. In addition, we have identified a conserved peptide motif that is required for this interaction. Our results imply that an ancient function of Myb in regulating G2/M genes in both plants and animals appears to have been transferred from the DNA-binding domain to the animal-specific C-terminal domain. Increased expression of B-MYB/MYBL2, the human ortholog of Drosophila Myb, correlates with poor prognosis in human patients with breast cancer. Therefore, our results imply that the specific interaction of the C terminus of Myb with the MuvB/dREAM core complex may provide an attractive target for the development of cancer therapeutics.
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Andrejka
authors.forename: Hong
authors.initials: H
authors.lastname: Wen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ashton
authors.forename: Megan
authors.initials: M
authors.lastname: Grant
authors.forename: Kevin
authors.initials: K
authors.lastname: Iori
authors.forename: Amy
authors.initials: A
authors.lastname: Wang
authors.forename: J Robert
authors.initials: JR
authors.lastname: Manak
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Lipsick
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005260:Female; D020570:Genes, myb; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020626:Oncogene Proteins v-myb / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C064352:MYBL2 protein, human; D050505:Mutant Proteins; D020626:Oncogene Proteins v-myb; D012097:Repressor Proteins; D015534:Trans-Activators