Translational activation of the non-AUG-initiated c-myc 1 protein at high cell densities due to methionine deprivation.
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.
Hann
S R
SR
Department of Cell Biology, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232-2175.
Sloan-Brown
K
K
Spotts
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GD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002452:Cell Count; D003062:Codon; D004247:DNA; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008715:Methionine / Q000172:deficiency / Q000502:physiology*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003062:Codon; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA; D008715:Methionine