Translational activation of the non-AUG-initiated c-myc 1 protein at high cell densities due to methionine deprivation.

Hann SR, Sloan-Brown K, Spotts GD
Genes Dev. 1992 6 (7): 1229-40

PMID: 1628829 · DOI:10.1101/gad.6.7.1229

c-myc belongs to a small, yet growing, group of eukaryotic mRNAs that initiate translation inefficiently from a non-AUG codon upstream from a more efficient AUG codon. We have examined the translational regulation of non-AUG-initiated c-myc 1 and AUG-initiated c-myc 2 protein synthesis in avian and mouse cells during proliferation. As lymphoid, erythroid, and embryo fibroblast cells approached high densities in culture, there was a sustained 5- to 10-fold induction in the synthesis of c-myc 1 protein to levels greater than or equal to c-myc 2 protein synthesis. Treatment with conditioned/depleted media from high-density cells was able to reproduce this activation in low-density cells within 5 hr. Additional studies with the conditioned/depleted media revealed that amino acid availability, specifically methionine deprivation, was responsible for this unique translational control. Our results describe a specific and dramatic regulation of dual translational initiation. Furthermore, these results represent a novel translational activation of a specific gene in higher eukaryotes in response to nutrient deprivation.

MeSH Terms (14)

Amino Acid Sequence Animals Base Sequence Cell Count Codon DNA Gene Expression Regulation Humans Kinetics Methionine Molecular Sequence Data Protein Biosynthesis Proto-Oncogene Proteins c-myc Tumor Cells, Cultured

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