Abstract
c-Myc plays a part in the regulation of important cellular processes such as growth, differentiation and neoplastic transformation1-3. Although c-myc gene structure and expression are well characterized1-3, the function and biochemical properties of the protein are less well understood4-6. Human c-myc is a 439-amino acid phos-phoprotein which binds DNA in vitro and belongs to a discrete subset of nuclear proteins1-3. Using the human c-myc mutants generated by linker-insertion and deletion mutagenesis, we have defined regions of the protein that are important for its transforming activities7 and its nuclear localization8. Here, we show that human c-myc exists as an oligomer in vitro and use mutant proteins to localize the oligomerization domain to a carboxyl-terminal peptide containing the 'leucine zipper' motif. The "leucine zipper' describes a structure found in a number of DNA-binding proteins that contains leucines occurring at intervals of every seventh amino acid in a region predicted to be α-helical9. The 'leucine zipper' might mediate dimerization by intermolecular interdigitation of the leucine side-chains. We show that a c-myc mutant, which is inactive but can oligomerize, dominantly inhibits the cotransform-ing activity with wild-type c-myc of rat embryo cells, whereas inactive mutants which cannot oligomerize properly because of deletions in the oligomerization domain are recessive.
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Dang, C., McGuire, M., Buckmire, M. et al. Involvement of the 'leucine zipper' region in the oligomerization and transforming activity of human c-myc protein. Nature 337, 664–666 (1989). https://doi.org/10.1038/337664a0
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DOI: https://doi.org/10.1038/337664a0
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