Cbl (also designated the c-Cbl proto-oncogene, E3 ubiquitin-protein ligase CBL ,Casitas B-lineage lymphoma proto-oncogene and RING finger protein 55) has been identified as the cellular homolog of the v-Cbl oncogene isolated from an NFS/N mouse that developed a pre-B cell lymphoma following infection with the replication-competent Cas Br-M murine leukemic virus. c-Cbl is expressed at relatively high levels in a wide range of hematopoietic tumor cell lines as well as in normal tissues such as thymus and testis. The c-Cbl gene product has been identified as a cytoplasmic protein with apparent DNA binding and dimerization domains characteristic of transcription factors. A single c-Cbl locus termed CBL2 has been mapped to human chromosome 11q23. This region of chromosome 11 is involved in translocations and deletions in a broad range of leukemias; c-Cbl has been found to be translocated from chromosome 11 in leukemias with either t(4;11) or t(11;14) abnormalities.