The Myb leucine zipper is essential for leukemogenicity of the v-Myb protein.
The AMV v-Myb oncoprotein causes oncogenic transformation of myelomonocytic cells in vivo and in vitro. Its transforming capacity is strictly dependent upon the N-terminal DNA binding domain, the central transactivation region, and on the C-terminal domain containing a putative leucine zipper motif. Here we show that the v-MybL3,4A mutant, in which Leu325 and Leu332 of the leucine zipper have been replaced by alanines, failed to induce leukemia in virus infected chicken. This demonstrates that the leucine zipper domain is indispensable for v-myb induced leukemogenesis in vivo. v-MybL3,4A was, however, still able to transform myelomonocytic cells from chicken bone marrow in vitro. Yet, while v-mybL3,4A transformed cells were impaired in growth at 37 degrees C, they failed to grow at 42 degrees C, the physiological body temperature of avian species. This might explain the loss of v-MybL3,4A leukemogenic potential in vivo. We also demonstrate that the v-Myb leucine zipper domain interacts in vitro with two host cell proteins, p26 and p28. This interaction is compromised in v-MybL3,4A indicating that binding of v-Myb to p26 and p28 might be important for the leukemogenic potential of v-Myb.
Bartůnek
P
P
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague.
Karafiát
V
V
Dvoráková
M
M
Záhorová
V
V
Mandíková
S
S
Zenke
M
M
Dvorák
M
M
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001353:Avian Leukosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002642:Chick Embryo; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics; D006133:Growth Substances / Q000494:pharmacology; D007930:Leucine / Q000235:genetics; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009000:Monocytes / Q000473:pathology; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism; D020626:Oncogene Proteins v-myb; D017434:Protein Structure, Tertiary; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D013696:Temperature; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D006133:Growth Substances; D009687:Nuclear Proteins; D020626:Oncogene Proteins v-myb; D015682:Retroviridae Proteins, Oncogenic; D007930:Leucine