Role of c-Myc on Erythroid Differentiation

OHMORI, Y., TANABE, J., TERASHIMA, M., SHOJI, W., TAKADA, S. and OBINATA, M. Role of c-Myc on Erythroid Differentiation. Tohoku J. Exp. Med., 1992, 168 (2), 203-210-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. -c-Myc; commitment; differentiation; dimerization domain; erythoroleukemia cells