Myb-induced transformation.
The c-myb protooncogene has been implicated in the development of avian and murine hematopoietic neoplasms of the myeloid and lymphoid lineages. The transcription factor encoded by this gene has a dual function in oncogenesis because it regulates genes that prevent apoptosis and genes involved in cellular proliferation. c-myb has repeatedly been a target of retroviral insertional mutagenesis. The most common mechanism by which retroviruses activate c-myb's oncogenic potential is by providing transcriptional control that results in constitutive expression, a feature that is consistent with the demonstration that ectopic expression of c-myb can prevent growth arrest of differentiating hematopoietic cells. In a less common mechanism of activation, carboxyl(C)-terminal truncation renders the c-Myb protein more stable and active in transcriptional transactivation. Interestingly, the ability of v-Myb, a product of the avian myeloblastosis virus (AMV), to cause rapid transformation of cells in vivo and in vitro can be explained by the combined effects of deregulated expression through the retroviral LTR, N- and C-terminal truncation, and activating mutations in its DNA binding domain. Although c-myb's involvement in human leukemia has been suggested, it has never been clearly established and should be investigated further.
Wolff
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Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892-4255, USA. LWOLFF@helix.nih.gov
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D009189:Avian Myeloblastosis Virus / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000235:genetics; D009154:Mutation; D020626:Oncogene Proteins v-myb; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D020626:Oncogene Proteins v-myb; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015682:Retroviridae Proteins, Oncogenic; D015534:Trans-Activators