Amino acid deprivation induces translation of branched-chain alpha-ketoacid dehydrogenase kinase.
Leucine, isoleucine, and valine are used by cells for protein synthesis or are catabolized into sources for glucose and lipid production. These branched-chain amino acids influence proteolysis, hormone release, and cell cycle progression along with their other metabolic roles. The branched-chain amino acids play a central role in regulating cellular protein turnover by reducing autophagy. These essential amino acids are committed to their catabolic fate by the activity of the branched-chain alpha-ketoacid dehydrogenase complex. Activity of the branched-chain alpha-ketoacid dehydrogenase complex is regulated by phosphorylation/inactivation of the alpha-subunit performed by a complex specific kinase. Here we show that elimination of the branched-chain amino acids from the medium of cultured cells results in a two- to threefold increased production of the branched-chain alpha-ketoacid dehydrogenase kinase with a decrease in the activity state of the branched-chain alpha-ketoacid dehydrogenase complex. The mechanism cells use to increase kinase production under these conditions involves recruitment of the kinase mRNA into polyribosomes. Promoter activity and the steady-state concentration of the mRNA are unchanged by these conditions.
Doering
C B
CB
Program in Genetics and Molecular Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Danner
D J
DJ
D000596:Amino Acids / Q000172:deficiency*; D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D002460:Cell Line; D006706:Homeostasis; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D012333:RNA, Messenger; D011494:Protein Kinases; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase