Mitosis-specific phosphorylation of the nuclear oncoproteins Myc and Myb.
The c-myc and c-myb proto-oncogenes encode phosphorylated nuclear DNA binding proteins that are likely to be involved in transcriptional regulation. Here we demonstrate that both Myc and Myb proteins are hyperphosphorylated during mitosis. In the case of Myb, hyperphosphorylation is accompanied by the appearance of three M phase-specific tryptic phosphopeptides. At least one of these phosphopeptides corresponds to a phosphopeptide generated after phosphorylation of Myb in vitro by p34cdc2 kinase. By contrast, the mitotic hyperphosphorylation of Myc does not correlate with the appearance of unique phosphopeptides, suggesting that M phase and interphase sites may be clustered within the same peptides. In addition Myc does not appear to be a target for p34cdc2 phosphorylation. The hyperphosphorylated forms of Myc and Myb from mitotic cells are functionally distinct from the corresponding interphase proteins in that the former have reduced ability to bind nonspecificially to double-stranded DNA cellulose. Furthermore, mitotic Myb binds poorly to oligodeoxynucleotides containing an Myb response element. We surmise that the decreased DNA binding capacity of hyperphosphorylated Myb and Myc during M phase may function to release these proteins from chromatin during chromosome condensation.
Lüscher
B
B
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Eisenman
R N
RN
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D008938:Mitosis; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA; D016203:CDC2 Protein Kinase; D015739:Nocodazole