title: Boron stress activates the general amino acid control mechanism and inhibits protein synthesis.
abstract: Boron is an essential micronutrient for plants, and it is beneficial for animals. However, at high concentrations boron is toxic to cells although the mechanism of this toxicity is not known. Atr1 has recently been identified as a boron efflux pump whose expression is upregulated in response to boron treatment. Here, we found that the expression of ATR1 is associated with expression of genes involved in amino acid biosynthesis. These mechanisms are strictly controlled by the transcription factor Gcn4 in response to boron treatment. Further analyses have shown that boron impaired protein synthesis by promoting phosphorylation of eIF2α in a Gcn2 kinase dependent manner. The uncharged tRNA binding domain (HisRS) of Gcn2 is necessary for the phosphorylation of eIF2α in the presence of boron. We postulate that boron exerts its toxic effect through activation of the general amino acid control system and inhibition of protein synthesis. Since the general amino acid control pathway is conserved among eukaryotes, this mechanism of boron toxicity may be of general importance.
authors: Izmir Institute of Technology, Department of Molecular Biology and Genetics, Izmir, Turkey.
authors: Irem
authors: I
authors: Uluisik
authors: Alaattin
authors: A
authors: Kaya
authors: Dmitri E
authors: DE
authors: Fomenko
authors: Huseyin C
authors: HC
authors: Karakaya
authors: Bradley A
authors: BA
authors: Carlson
authors: Vadim N
authors: VN
authors: Gladyshev
authors: Ahmet
authors: A
authors: Koc
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D049148:Aminoacylation / Q000187:drug effects; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001895:Boron / Q000009:adverse effects*; D020869:Gene Expression Profiling; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012343:RNA, Transfer; D060888:Real-Time Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: C108080:ATR1 protein, S cerevisiae; D000596:Amino Acids; D050976:Basic-Leucine Zipper Transcription Factors; D015415:Biomarkers; C501391:GCN4 protein, S cerevisiae; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer; C512912:GCN2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D001895:Boron