Role of c-Myc on erythroid differentiation.
In the early event of the induction of mouse erythroleukemia (MEL) cell differentiation, c-myc mRNA levels show a biphasic change. The elevated expression of a transfected c-myc gene inhibits the commitment and differentiation of MEL cell transformants. In the present work, we have introduced human c-myc mutants into MEL cells under the inducible promoter to define the functional domains of c-Myc involved in erythroid differentiation. The c-Myc domains necessary for commitment and differentiation are not colocalized; almost entire regions are required for inhibition of commitment, whereas domains II and IV that are essential for co-transforming activity with ras are required for inhibition of differentiation. Interestingly, mutants that delete domains for c-Myc dimerization motifs enhanced differentiation. Thus, c-Myc interferes with MEL cell differentiation by interacting with c-Myc partners and the induced protein(s) through dimerization domains. These results suggest that c-Myc may regulate commitment and differentiation by interacting with proteins through different domains.
Ohmori
Y
Y
Department of Cell Biology, Tohoku University, Sendai, Japan.
Tanabe
J
J
Terashima
M
M
Shoji
W
W
Takada
S
S
Obinata
M
M
D000818:Animals; D001704:Biopolymers; D002454:Cell Differentiation / Q000235:genetics; D016259:Genes, myc; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D051379:Mice; D009154:Mutation; D010641:Phenotype; D014407:Tumor Cells, Cultured
D001704:Biopolymers