Isolation of the proto-oncogene c-myb from D. melanogaster

Katzen, Alisa L.; Kornberg, Thomas B.; Bishop, J. Michael

doi:10.1016/s0092-8674(85)80018-0

Cited by 151 publications

(107 citation statements)

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“…Several temperature-sensitive and null alleles of Drosophila Myb have previously been described (17)(18)(19)(20). However, attempts to isolate additional mutant alleles via traditional chemical mutagenesis were unsuccessful despite the screening of large numbers of mutagenized animals.…”

Section: Evolutionarily Guided Alanine Substitution Mutants Of Drosopmentioning

confidence: 99%

Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex

Andrejka

Wen

Ashton

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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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.oncogene | transcription | repression | evolution T he Myb oncogene family was discovered because of the retroviral transduction of the chicken cellular myb protooncogene that generated the avian myeloblastosis virus (1, 2). Both the cellular Myb and viral Myb proteins are present within the nucleus of the cell, bind to specific DNA sequences, and can regulate gene expression (3-9). The Myb DNA-binding domain is present in members of all major classes of eukaryotic organisms, including plants, animals, fungi, cellular slime molds, and protists (10, 11). Simpler plants have only one or a few Myb transcription factors, whereas all flowering plant species have hundreds of related Myb transcription factors that arose via massive gene duplication and divergence (12). The picture in animals is simpler. All vertebrates have three closely related Myb transcription factors, whereas most invertebrates have only one Myb transcription factor. In addition to the presence of an aminoterminal Myb DNA-binding domain, most of these Myb transcription factors of animals share a conserved C-terminal domain that appears to be animal-specific. We have recently reported that, rather surprisingly, this C-terminal Myb domain is sufficient to rescue the lethality of a Myb null mutation in Drosophila when expressed via a heterologous promoter (13). We have now used a combination of genetic, cell biological, and biochemical approaches to explore the function of this animal-specific C-terminal Myb domain. We find that this domain is both necessary and sufficient for interaction with the synthetic multivulval class B (MuvB) core, a highly conserved transcriptional repressor complex that also interacts with the E2F-Rb tumor suppressor proteins (14-16...

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Section: Evolutionarily Guided Alanine Substitution Mutants Of Drosopmentioning

confidence: 99%

Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex

Andrejka

Wen

Ashton

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…This nucleotide sequence data has been subrnitted to DDBJ, EMBL, and GenBank as accession number D14712. Katzen et al, 1985), and human c-MYB (HCMYB;Majelloet al, 1986). Shaded boxes indicate amino acid residues identical to those of ATMYBP, and asterisks represent conserved tryptophan residues.…”

Section: Cloning and Sequence Analysis Of A Myb-related Gene From Aramentioning

confidence: 99%

“…Six and seven different cDNAs for myb homologs have been reported in Antirrhinum and Arabidopsis, respectively (Jackson et al, 1991;Oppenheimer et al, 1991;. By contrast, only one and three genes for myb homologs have been cloned from Drosophila and humans, respectively (Katzen et al, 1985;Nomura et al, 1988). Thus, plant myb-related genes constitute a rather large family of genes and may play a wide variety of roles in the regulation of gene expression.…”

Section: Introductionmentioning

confidence: 99%

An Arabidopsis myb homolog is induced by dehydration stress and its gene product binds to the conserved MYB recognition sequence.

et al. 1993

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An Arabidopsis cDNA (Atmyb2) that contains a sequence that encodes a transcription factor, which is a homolog of MYB, was cloned from a cDNA library prepared from dehydrated Arabidopsis rosette plants. A gene (AtmybP) corresponding to the Atmyb2 cDNA was also cloned and its nucleotide sequence was determined. RNA gel blot analysis showed that the AtmybP mRNA was induced by dehydration and dísappeared upon rehydration. The Atmyb2 mRNA also accumulated upon salt stress and with the onset of treatment with abscisic acid. A Pglucuronidase reporter gene driven by the AtmybP promoter was induced by dehydration and salt stress in transgenic Arabidopsis plants. These observations indicate that AtmybP is responsive to dehydration at the transcriptional level. The putative protein (ATMYB2) encoded by AtmybP has 274 amino acids, a molecular m a s of 32 kD, and a putative DNA binding domain that shows considerable homology to plant MYB-related proteins, such as maize C1. A fusion protein that included ATMYBP was expressed in Escherichia coli, and it bound specifically to oligonucleotides that contained a consensus MYB recognition sequence (TAACTG), such as is found in the simian virus 40 enhancer and the maize bronze1 promoter. Binding was sequence specific, as indicated by a gel mobility shift experiment. These results suggest that a MYB-related transcription factor is involved in the regulation of genes that are responsive to water stress in Arabidopsis.

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“…Near the carboxyl terminus of the ~1 proteins, however, are two conserved tryptophan residues spaced 19 residues apart, and such residues and spacing are characteristic of the DNA-binding domain of Myb proteins (Frampton et al 1991) and Ets proteins (Macleod et al 1992). In K1 ~1, one of these tryptophans is part of the sequence NWELIA, which is highly similar to NWEIIG of Drosophila Myb and DWTLIA of human A Myb (Katzen et al 1985;N o m u r a et al 1988). Other conserved features of Myb or Ets proteins, though, do not appear to be present in the ~1 proteins.…”

Section: The Matcxl Homologmentioning

confidence: 99%

Coupling of cell identity to signal response in yeast: interaction between the alpha 1 and STE12 proteins.

Yuan¹,

Stroke²,

Fields³

1993

Genes Dev.

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In Saccharomyces cerevisiae, the STE12 protein mediates transcriptional induction of cell type-specific genes in response to pheromones. STE12 binds in vitro to the pheromone response elements (PREs) present in the control region of a-specific genes. STE12 is also required for transcription of o~-specific genes, but there is no evidence that it binds directly to these genes. Instead, the MAToL-encoded protein o~l and the MCM1 product bind to the DNA element that is responsible for ,v-specific and a-factor-inducible expression. To explore the role of STE12 in the pheromone induction of ,v-specific genes, we cloned STE12 and MATal homologs from the related yeast Kluyveromyces lactis. The K. lactis STE12 protein did not cooperate with the S. cerevisiae od protein to promote the overall mating process or the induction of transcription of an s-specific gene. However, introduction of both K. lactis STE12 along with K. lactis od did restore mating, suggesting that an interaction between STE12 and ~1 is important for s-specific gene activation. We also show that bacterially expressed STE12 and r are able to form a complex in vitro. Thus, we demonstrate a coupling in ~ cells between a protein functioning in cell identity, ~1, with a protein responsive to the pheromone-induced signal STE12.

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Isolation of the proto-oncogene c-myb from D. melanogaster

Cited by 151 publications

References 52 publications

Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex

Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex

An Arabidopsis myb homolog is induced by dehydration stress and its gene product binds to the conserved MYB recognition sequence.

Coupling of cell identity to signal response in yeast: interaction between the alpha 1 and STE12 proteins.

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