THE MYB LEUCINE-ZIPPER IS ESSENTIAL FOR LEUKEMOGENICITY OF THE V-MYB PROTEIN

The AMV v-Myb oncoprotein causes oncogenic transformation of myelomono cytic cells in vivo and in vitro, Its transforming capacity is strictl y dependent upon the N-terminal DNA binding domain, the central transa ctivation region, and on the C-terminal domain containing a putative l eucine zipper motif, Here we show that the v-Myb(L3.4A) mutant, in whi ch Leu(325) and Leu(332) of the leucine zipper have been replaced by a lanines, failed to induce leukemia in virus infected chicken, This dem onstrates that the leucine zipper domain is indispensable for v-myb in duced leukemogenesis in vivo, v-Myb(L3,3A) was, however, still able to transform myelomonocytic cells from chicken bone marrow in vitro. Yet , while v-myb(L3,4) transformed cells were impaired in growth at 37 de grees C, they failed to grow at 42 degrees C, the physiological body t emperature of avian species, This might explain the loss of v-Myb(L3,4 A) 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) indicatin g that binding of v-Myb to p26 and p28 might be important for the leuk emogenic potential of v-Myb.