Oncogenic mutations cause dramatic, qualitative changes in the transcriptional activity of c-Myb

Liu, F; Lei, Wenliang; O'Rourke, John P.; Ness, Scott A.

doi:10.1038/sj.onc.1209105

Cited by 41 publications

(61 citation statements)

References 39 publications

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“…This is consistent with the idea that v-Myb regulates only a subset of genes regulated by c-Myb (14). Microarray analyses of human cells transfected with versions of Myb carrying subsets of the oncogenic amino acid replacements have revealed a group of c-Myb-regulated genes whose activation was dependent on the mutant status of the transactivation region similar to the mim-1 gene (14). Possibly, these genes represent a class of c-Myb target genes whose acti- vation requires major changes in the nucleosomal architecture, as exemplified by the mim-1 enhancer.…”

Section: Amino Acid Substitutions In the Central Region Of V-myb Contsupporting

confidence: 79%

“…By suffering the point mutations v-Myb was apparently selected for its failure to activate this differentiation program, thereby raising its oncogenic potential. This is consistent with the idea that v-Myb regulates only a subset of genes regulated by c-Myb (14). Microarray analyses of human cells transfected with versions of Myb carrying subsets of the oncogenic amino acid replacements have revealed a group of c-Myb-regulated genes whose activation was dependent on the mutant status of the transactivation region similar to the mim-1 gene (14).…”

Section: Amino Acid Substitutions In the Central Region Of V-myb Contsupporting

confidence: 70%

“…In addition, the v-Myb protein of AMV harbors several amino acid substitutions that were acquired during the passage of the virus and strongly enhance its oncogenic potential (15). These "oncogenic" substitutions have raised considerable interest because they exert drastic effects on the activity of v-Myb and the spectrum of its target genes (14,16). Some of the oncogenic substitutions are located in the DNA binding domain and affect the interaction of v-Myb with DNA (17,18) and other proteins (19 -21).…”

mentioning

confidence: 99%

“…A variety of approaches has been used to identify Myb target genes, such as differential screening of cells transformed by a temperature-sensitive mutant of v-Myb (7), differential display of RNA from cells expressing estrogen-inducible or dominant-interfering versions of v-Myb or c-Myb (10 -12) or microarray-based assays of cells overexpressing different Myb family members (13,14). Although a growing number of Myb target genes are now known, how they contribute to the biological effects of Myb is not fully understood.…”

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confidence: 99%

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Myb-induced Chromatin Remodeling at a Dual Enhancer/Promoter Element Involves Non-coding RNA Transcription and Is Disrupted by Oncogenic Mutations of v-myb

Wilczek

Chayka²,

Plachetka

et al. 2009

Journal of Biological Chemistry

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The oncogene v-myb of avian myeloblastosis virus (AMV) encodes a transcription factor (v-Myb) that transforms myelomonocytic cells by deregulating the expression of specific target genes. v-myb has acquired its oncogenic potential by truncation as well as by a number of point mutations of its cellular progenitor c-myb. As a result of these changes, the target gene spectrum v-Myb differs from that of c-Myb. We recently showed that the chicken mim-1 gene, a c-Myb target gene that is not activated by v-Myb harbors a powerful cell type-specific and Myb-inducible enhancer in addition to a Myb-responsive promoter. We now show that Myb-dependent activation of the mim-1 gene is accompanied by extensive remodeling of the nucleosomal architecture at the enhancer. We found that the mim-1 enhancer region also harbors a promoter whose activity is stimulated by Myb and which directs the transcription of an apparently non-coding RNA. Furthermore, our data show that the oncogenic mutations of AMV have disrupted the ability of v-Myb to induce remodeling of chromatin structure at the mim-1 enhancer. Together, our results demonstrate for the first time directly that Myb induces alterations of the nucleosomal organization at a relevant target site and provide new insight into the functional consequences of the oncogenic amino acid substitutions.

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Section: Amino Acid Substitutions In the Central Region Of V-myb Contsupporting

confidence: 79%

Section: Amino Acid Substitutions In the Central Region Of V-myb Contsupporting

confidence: 70%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Myb-induced Chromatin Remodeling at a Dual Enhancer/Promoter Element Involves Non-coding RNA Transcription and Is Disrupted by Oncogenic Mutations of v-myb

Wilczek

Chayka²,

Plachetka

et al. 2009

Journal of Biological Chemistry

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“…Consequently, a large number of genes have been shown to be regulated by c-Myb, including genes involved in proliferation, cell survival and differentiation. [11][12][13] One of the most strongly activated Myb target genes is the chicken myb-inducible myeloid-specific gene-1 (mim-1), originally identified by Ness et al 14 Recent work has shown that mim-1 expression is regulated by Myb in a complex manner, involving several cis-acting DNA-elements, as well as several cooperating proteins. [15][16][17][18][19] Although myb was originally identified as the oncogene of the avian myeloblastosis virus, it was suspected that c-myb is also involved in the development of human cancer.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Myb-dependent gene expression by the sesquiterpene lactone mexicanin-I

et al. 2011

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Melanocyte fate in neural crest is triggered by Myb proteins through activation of c-kit

Karafiát

Dvořáková

Pajer

et al. 2007

Cell. Mol. Life Sci.

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The c-myb proto-oncogene and its oncogenic derivative v-mybAMV encode transcriptional regulators engaged in the commitment of hematopoietic cells. While the c-Myb protein is important for the formation and differentiation of various progenitors, the v-MybAMV oncoprotein induces in chicks a progression and transformation of the single (monoblastic) cell lineage. Here we present the first evidence of cell fate-directing abilities of c-Myb and v-MybAMV proteins in avian neural crest (NC), where both proteins determine melanocytogenesis. The increased concentration of c-Myb induces progression into dendritic melanocytes and differentiation. The v-myb oncogene converts essentially all NC cells into melanocytes and causes their transformation. Both Myb proteins activate in NC cells expression of the c-kit gene and stem cell factor c-Kit signaling--one of the essential pathways in melanocyte development. These observations suggest that the c-myb-c-kit pathway represents a common regulatory scheme for both hematopoietic and neural progenitors and establishes a novel experimental model for studies of melanocytogenesis and melanocyte transformation.

show abstract

Oncogenic mutations cause dramatic, qualitative changes in the transcriptional activity of c-Myb

Cited by 41 publications

References 39 publications

Myb-induced Chromatin Remodeling at a Dual Enhancer/Promoter Element Involves Non-coding RNA Transcription and Is Disrupted by Oncogenic Mutations of v-myb

Myb-induced Chromatin Remodeling at a Dual Enhancer/Promoter Element Involves Non-coding RNA Transcription and Is Disrupted by Oncogenic Mutations of v-myb

Inhibition of Myb-dependent gene expression by the sesquiterpene lactone mexicanin-I

Melanocyte fate in neural crest is triggered by Myb proteins through activation of c-kit

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