The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif.
The murine Cas NS-1 retrovirus carries the v-cbl oncogene and induces pre-B cell lymphomas and myeloid leukemias. The cellular homolog of v-cbl has been identified in mouse and human DNA, and was recently mapped to mouse chromosome 9 and human chromosome 11q23. To determine the coding sequences of the human and mouse c-cbl proto-oncogenes cDNA clones were isolated from libraries prepared from the human T cell leukemia lines CCRF-CEM and HUT 78, and the mouse pre-B cell line 70Z/3. DNA sequencing revealed an open reading frame encoding 906 amino acids in the human cDNAs and 896 amino acids in 70Z/3. The sequence showed that v-cbl is a markedly truncated form of murine c-cbl containing 355 N-terminal amino acids. The nucleotide sequence of v-cbl is identical to murine c-cbl in this region, and the human sequence has only five amino acid changes in the v-cbl portion. The most notable features of the sequence which was lost in the generation of v-cbl is a C-terminal leucine zipper and a stretch of 208 amino acids containing 23% proline and 19% serine/threonine residues. This proline-rich sequence has similarities to the transcriptional activation domains of some transcription factors, and v-cbl's transforming potential may be due to the loss of this region and the leucine zipper.
Blake
T J
TJ
Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, Australia.
Shapiro
M
M
Morse
H C
HC
Langdon
W Y
WY
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D015723:Gene Library; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D050722:Oncogene Protein v-cbl; D016366:Open Reading Frames; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl; D015183:Restriction Mapping; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014170:Transformation, Genetic; D044767:Ubiquitin-Protein Ligases
D050722:Oncogene Protein v-cbl; D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human; C493849:Cbl protein, mouse