A rearrangement of the c-cbl proto-oncogene in HUT78 T-lymphoma cells results in a truncated protein

Abstract

The murine Cas NS-1 retrovirus carries the v-cbl oncogene and induces pro-B, pre-B and myeloid tumors in mice inoculated at birth. The human homolog of v-cbl is located on chromosome 11q23.3, which is in the region of translocation breakpoints in a range of acute leukemias. The sequencing of the human and murine c-cbl proto-oncogenes has revealed v-cbl as a markedly truncated form of c-cbl that encompasses 40% of the amino terminus. This truncation deletes a proline- and serine/threonine-rich domain and a putative leucine zipper. In this study we describe the nature of a truncated form of c-cbl present in the cutaneous T-cell lymphoma line HUT78. In these cells a genetic rearrangement involving unknown sequences and Alu repeat sequences results in the insertion of a premature stop codon that removes 259 amino acids from the carboxy terminus. This results in the translation of a 72 kDa protein, compared with the 120 kDa protein encoded by full-length c-cbl, which lacks a portion of the proline-rich domain and the entire leucine zipper.