Myb DNA binding inhibited by phosphorylation at a site deleted during oncogenic activation.
The c-Myb nuclear oncoprotein is phosphorylated in vitro and in vivo at an N-terminal site near its DNA-binding domain by casein kinase II (CK-II) or a CK-II-like activity. This in vitro phosphorylation reversibly inhibits the sequence-specific binding of c-Myb to DNA. The site of this phosphorylation is deleted in nearly all oncogenically activated Myb proteins, resulting in DNA-binding that is independent of CK-II. Because CK-II activity is modulated by growth factors, loss of the site could uncouple c-Myb from its normal physiological regulator.
Lüscher
B
B
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Christenson
E
E
Litchfield
D W
DW
Krebs
E G
EG
Eisenman
R N
RN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D047388:Casein Kinases; D002460:Cell Line; D002645:Chickens; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007163:Immunosorbent Techniques; D009052:Leukemia Virus, Murine / Q000235:genetics; D007942:Leukemia, Experimental / Q000378:metabolism; D008969:Molecular Sequence Data; D009857:Oncogenes; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D011494:Protein Kinases; D047388:Casein Kinases