AMPK represses TOP mRNA translation but not global protein synthesis in liver.
The AMP-activated protein kinase (AMPK) represses signaling through the mammalian target of rapamycin complex 1 (mTORC1). In muscle, repression of mTORC1 leads to a reduction in global protein synthesis. In contrast, repression of mTORC1 in the liver has no immediate effect on global protein synthesis. In the present study, signaling through mTORC1 and translation of specific mRNAs such as those bearing a 5'-terminal oligopyrimidine (TOP) tract and were examined in rat liver following activation of AMPK after treadmill running. Activation of AMPK repressed translation of the TOP mRNAs encoding rpS6, rpS8, and eEF1alpha. In contrast, neither global protein synthesis nor translation of mRNAs encoding GAPDH or beta-actin was changed. Basal phosphorylation of the mTORC1 target 4E-BP1, but not S6K1 or rpS6, was reduced following activation of AMPK. Thus, in liver, AMPK activation repressed translation of TOP mRNAs through a mechanism distinct from downregulated phosphorylation of S6K1 or rpS6.
Reiter
Ali K
AK
Department of Cellular and Molecular Physiology, The Pennsylvania State College of Medicine, PO Box 850, Hershey, PA 17033, USA.
Bolster
Douglas R
DR
Crozier
Stephen J
SJ
Kimball
Scot R
SR
Jefferson
Leonard S
LS
D055372:AMP-Activated Protein Kinases; D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D005080:Exercise Test; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D038641:RNA 5' Terminal Oligopyrimidine Sequence / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038601:Ribosomal Protein S6 / Q000096:biosynthesis / Q000235:genetics; D019893:Ribosomal Protein S6 Kinases / Q000096:biosynthesis / Q000235:genetics; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D000199:Actins; C519510:Crtc1 protein, rat; D009097:Multienzyme Complexes; D020648:Peptide Elongation Factor 1; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D014157:Transcription Factors; C030254:ribosomal protein S8; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; C526901:Rps6kb1 protein, rat; D055372:AMP-Activated Protein Kinases