Enhanced translation and increased turnover of c-myc proteins occur during differentiation of murine erythroleukemia cells.

Spotts GD, Hann SR
Mol Cell Biol. 1990 10 (8): 3952-64

PMID: 2196440 · PMCID: PMC360906 · DOI:10.1128/mcb.10.8.3952

To determine whether regulation of c-myc proteins occurs during the differentiation of murine erythroleukemia cells, we examined c-myc protein synthesis and accumulation throughout dimethyl sulfoxide (DMSO)- or hypoxanthine-induced differentiation. c-myc protein expression exhibited an overall biphasic reduction, with an initial concomitant decrease in c-myc RNA, protein synthesis, and protein accumulation early during the commitment phase. However, as the mRNA and protein levels recovered, c-myc protein synthesis levels dissociated from the levels of c-myc mRNA and protein accumulation. This dissociation appears to result from unusual translational and posttranslational regulation during differentiation. Translational enhancement was suggested by the observation that relatively high levels of c-myc proteins were synthesized from relatively moderate levels of c-myc RNA. This translational enhancement was not observed with c-myb. Under certain culture conditions, we also observed a change in the relative synthesis ratio of the two independently initiated c-myc proteins. Posttranslational regulation was evidenced by a dramatic postcommitment decrease in the accumulated c-myc protein levels despite relatively high levels of c-myc protein synthesis. This decrease corresponded with a twofold increase in the turnover of c-myc proteins. The consequence of this regulation was that the most substantial decrease in c-myc protein accumulation occurred during the postcommitment phase of differentiation. This result supports the hypothesis that the reduction in c-myc at relatively late times is most important for completion of murine erythroleukemia cell terminal differentiation.

MeSH Terms (20)

Animals Blotting, Western Cell Differentiation Cell Line Dimethyl Sulfoxide Gene Expression Hypoxanthine Hypoxanthines Kinetics Leukemia, Erythroblastic, Acute Leukemia, Experimental Mice Protein-Tyrosine Kinases Protein Biosynthesis Protein Processing, Post-Translational Proto-Oncogene Proteins Proto-Oncogene Proteins c-myc RNA, Messenger RNA, Neoplasm Time Factors

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