The leucine zipper of c-Myc is required for full inhibition of erythroleukemia differentiation.
The leucine zipper motif has been observed in a number of proteins thought to function as eucaryotic transcription factors. Mutation of the leucine zipper interferes with protein dimerization and DNA binding. We examined the effect of point mutations in the leucine zipper of c-Myc on its ability to dimerize in vitro and to inhibit Friend murine erythroleukemia (F-MEL) differentiation. Glutaraldehyde cross-linking studies failed to provide evidence for homodimerization of in vitro-synthesized c-Myc protein, although it was readily demonstrated for c-Jun. Nevertheless, whereas transfected wild-type c-myc sequences strongly inhibited F-MEL differentiation, those with single or multiple mutations in the leucine zipper were only partially effective in this regard. Since the leucine zipper domain of c-Myc is essential for its cooperative effect in ras oncogene-mediated transformation, this study emphasizes the close relationship that exists between transformation and hematopoietic commitment and differentiation. c-Myc may produce its effects on F-MEL differentiation through leucine zipper-mediated heterodimeric associations rather than homodimeric ones.
Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor 48109.
M J
MJ
Smith
D C
DC
Charron-Prochownik
E V
EV
Prochownik
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004920:Erythropoiesis; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc