Increase in specific DNA binding by carboxyl truncation suggests a mechanism for activation of Myb.
Oncogenic forms of the c-myb protein (Myb) often exhibit amino-terminal and/or carboxyl-terminal truncations. When the transcriptional activity of these proteins was examined it was found that carboxyl-truncated Myb is more effective as a transcriptional activator than full-length or amino-truncated Myb. In order to determine the effect of such truncations on sequence-specific DNA binding, we synthesized murine Myb in vitro and assessed DNA binding by using a mobility-shift assay. Compared with the full-length protein no difference in binding was observed following deletion of the amino terminus, despite the removal of much of the first repeat of the DNA-binding domain. However, the specific DNA-binding capacity of carboxyl-truncated Myb was 4-6 times greater than that of the full-length protein; moreover, DNA binding was independent of a 'leucine zipper' motif present in Myb. These observations suggest that the increased transforming and transactivating potential of carboxyl-truncated Myb is due, at least in part, to increased sequence-specific DNA binding.
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Parkville, Australia.
R G
RG
Ramsay
S
S
Ishii
T J
TJ
Gonda
D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D004247:DNA