The v‐cbl oncogene is the transforming gene of the murine Cas NS‐1 retrovirus which induces pre‐B cell lymphomas and myeloid leukaemias. Sequencing of c‐cbl has revealed that v‐cbl was generated by a large truncation that removed 60% of the C‐terminus of the corresponding protein. In this study we prepared antibodies to cbl and found that c‐cbl encodes a 120 kDa protein which is localized in the cytoplasm with a cytosolic and cytoskeletal distribution. Immunofluorescence studies show a striking pattern of brightly staining vesicles in mitotic cells similar to that observed with cytokeratin antibodies. In contrast to p120c‐cbl, which is exclusively cytoplasmic, the p100gag‐v‐cbl encoded by Cas NS‐1 is localized in both the cytoplasm and the nucleus. This redistribution to the nucleus correlates with the ability of cbl to induce acute transformation. Furthermore the truncated protein encoded by v‐cbl can bind DNA, unlike the full‐length protein. These results suggest that the C‐terminus of cbl is involved in the retention of p120c‐cbl in the cytoplasm and the inhibition of DNA binding. The findings also suggest that a truncated protein encoded by c‐cbl exists in the nucleus of normal cells.

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