Methylglyoxal activates Gcn2 to phosphorylate eIF2alpha independently of the TOR pathway in Saccharomyces cerevisiae.
Methylglyoxal is a ubiquitous 2-oxoaldehyde derived from glycolysis. Previously, we have reported that methylglyoxal attenuates the rate of overall protein synthesis in Saccharomyces cerevisiae through phosphorylation of the alpha subunit of translation initiation factor 2 (eIF2alpha) in a Gcn2-dependent manner. Phosphorylation of eIF2alpha impedes the formation of a translation initiation complex, and subsequently, overall protein synthesis is reduced. Uncharged tRNA plays an important role in the activation of Gcn2, although we found that MG treatment did not elevate the levels of uncharged tRNA. Rapamycin, a potent inhibitor of TOR kinase, is known to induce phosphorylation of eIF2alpha without affecting the levels of uncharged tRNA. We determined the correlation between methylglyoxal and TOR kinase activity and found that phosphorylation of eIF2alpha by methylglyoxal occurred independently of the target of rapamycin (TOR) pathway.
Nomura
Wataru
W
Laboratory of Molecular Microbiology, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, 611-0011, Japan.
Maeta
Kazuhiro
K
Kita
Keiko
K
Izawa
Shingo
S
Inoue
Yoshiharu
Y
D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism* / Q000494:pharmacology; D012331:RNA, Fungal / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
D015852:Eukaryotic Initiation Factor-2; C451460:FUN12 protein, S cerevisiae; C071664:GLN3 protein, S cerevisiae; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011765:Pyruvaldehyde; D012343:RNA, Transfer; C071570:SNF1-related protein kinases; C512912:GCN2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C500749:target of rapamycin protein, S cerevisiae; D020123:Sirolimus