Nucleotide sequence of chicken c-myb complementary DNA and implications for myb oncogene activation

Abstract

Avian myeloblastosis virus (AMV), like other acute transforming viruses, arose by recombination between its helper virus and host cellular sequences. The latter sequences, termed v-myb, are responsible for the oncogenic properties of the virus. AMV causes acute myeloblastic leukaemia in chickens and transforms a specific class of haematopoietic cells in vitro, but does not induce morphological transformation of cultured fibroblasts, suggesting that only a restricted target-cell population is responsive to its transforming gene product. The normal cellular counterpart of v-myb, c-myb, is highly conserved and is present in all vertebrate and some invertebrate species examined. DNA rearrangements and altered expression of the myb oncogene have been reported in mouse lymphoid tumours and human myeloid and colon tumours. The mechanism of activation of the cellular proto-oncogenes is thought to involve the structural alteration of the coding regions that result in either the synthesis of an altered gene product or the enhanced expression of a proto-oncogene caused by alterations in its regulatory elements. To distinguish between these two mechanisms, we have cloned and sequenced the chicken c-myb complementary DNA and compared it with that of v-myb sequences. We demonstrate that during the transduction of the cellular sequences and/or viral passage a substantial portion of the coding region of the c-myb gene has been lost from both the 5' and 3' ends, resulting in the generation of a truncated gene product that mediates the transforming function of the virus.

Identification of functional domains in the maize transcriptional activator C1: comparison of wild-type and dominant inhibitor proteins.

“…These results, together with the results discussed above, provide in vivo evidence that the product of the Cl gene functions as a transcriptional activator that utilizes a myb-like DNAbinding domain with an acidic transcriptional activation domain. The basic domain of myb oncogene products consists of three imperfect repeats of 51-52 amino acids (Gerondakis and Bishop 1986;Rosson and Reddy 1986), and this domain has been shown to bind both specifically and nonspecifically to DNA (Oehler et al 1990). Deletion analysis of the myb DNA-binding region was used to demonstrate that the first repeat (missing from the maize Cl protein) is not essential for DNA binding, whereas the second and third repeats are crucial for specific site recognition (Howe et al 1990;Oehler et al 1990).…”

Activation of transcription by v-myb: evidence for two different mechanisms.

“…Genes encoding similar domains have been identified in vertebrates (Gonda and Bishop 1983;Gonda et al 1985;Bender and Kuehl 1986;Gerondakis and Bishop 1986;Rosson and Reddy 1986;Slamon et al 1986), in insects (Katzen et al 1985;Peters et al 1987), and in plants (Paz-Ares et al 1987). The 2nyb-related clgene of Zea mays (Paz-Ares et al 1987) has been defined genetically as a regulator of genes, which are involved in anthocyanin biosynthesis.…”

Constitutive c-myb Expression in K562 Cells Inhibits Induced Erythroid Differentiation but Not Tetradecanoyl Phorbol Acetate-Induced Megakaryocytic Differentiation

“…Both viruses contain transduced cellular sequences which are an internal subset of the c-myb proto-oncogene (9,31). v-myb has thus acquired both 5Ј and 3Ј deletions that are associated with its transforming activity.…”