Studium variabilního úseku onkoproteinu v-Myb

Abstract

- 4 - Study of the v-Myb oncoprotein variable region The aim of this thesis was to analyze the significance of the variable region of oncoprotein v-Myb. The v-myb oncogene originated in the chick through a natural recombination of the MAV1 retroviral genome with the c-myb gene, which is an important transcriptional regulator involved in hematopoiesis and other important processes in different types of vertebrate cells. In comparison with the c-myb coding sequence, the retroviral v-myb is truncated on N- and C-terminals and includes 11 point mutations. Due to both these changes and the retroviral promoter which drives its expresion, the v-Myb oncoprotein became the inducer of acute myeloid leukemia in chicks. The variable region of v-Myb lies in between the N-terminal DNA binding and the central transactivating domains. This region is the least evolutionarily conserved part of the protein. No published data are available about its potential function. In this work the biological significance of the variable region was studied by means of specific deletions and sequence swaps. Two deletions (∆PstI and ∆NaeI) and two swaps (chicken v-myb to mouse and Xenopus c-myb) were prepared. Recombinant DNAs were cloned into MAV1-based retroviral vector and transfected into chick embryo fibroblasts (CEFs) in tissue...