The Myb leucine zipper is essential for leukemogenicity of the v-Myb protein

Abstract

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 Here we show that the v-Myb^L3,4A mutant, in which Leu³²⁵ and Leu³³² of the leucine zipper have been replaced by alanines, failed to induce leukemia in virus infected chicken.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-Myb^L3,4A was, however, still able to transform myelomonocytic cells from chicken bone marrow in vitro. Yet, while v-myb^L3,4A transformed cells were impaired in growth at 37°C, they failed to grow at 42°C, the physiological body temperature of avian species. This might explain the loss of v-Myb^L3,4A 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-Myb^L3,4A indicating that binding of v-Myb to p26 and p28 might be important for the leukemogenic potential of v-Myb.