A rearrangement of the c-cbl proto-oncogene in HUT78 T-lymphoma cells results in a truncated protein.
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.
Blake
T J
TJ
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, South Australia.
Langdon
W Y
WY
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D003001:Cloning, Molecular; D015321:Gene Rearrangement; D006801:Humans; D016399:Lymphoma, T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D010443:Peptide Chain Termination, Translational; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D014178:Translocation, Genetic; D044767:Ubiquitin-Protein Ligases
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human