異性化タンパク質修復酵素ＰＩＭＴの細胞機能における役割

DOI DOI Web Site Web Site PubMed 被引用文献3件 参考文献47件 オープンアクセス

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タイトル別名
  • The Role of Isomerized Protein Repair Enzyme, PIMT, in Cellular Functions
  • イセイカ タンパクシツ シュウフク コウソ PIMT ノ サイボウ キノウ ニ オケル ヤクワリ
  • ChemInform Abstract: The Role of Isomerized Protein Repair Enzyme, PIMT, in Cellular Functions

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説明

  Proteins are subject to various types of spontaneous modifications that can disrupt their structures with sometimes adverse affects on biological activity. The formation of L-isoaspartyl (or D-aspartyl) residues, through either the deamidation of asparagine or dehydration of aspartate, is one of the most frequent types of deterioration occurring under physiological conditions. Protein L-isoaspartate/D-aspartate o-methyltransferase (PIMT) is a conserved and ubiquitous enzyme that participates in the repair of various isomerized proteins. PIMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine onto the α-carboxyl group of an L-isoaspartyl (or the β-carboxyl group of an D-aspartyl) residue, which initiates the conversion of this residue to an L-aspartyl residue. PIMT-deficient mice have been shown to die at a mean age of 42 days from progressive epileptic seizures with grand mal and myoclonus. Although PIMT-deficiency clearly leads to the accumulation of isomerized proteins, it is currently unclear how this causes progressive epilepsy in PIMT-deficient mice. As a first step towards understanding this, we developed a new assay to measure PIMT activity in cell lysates. Additionally, we isolated PIMT knockdown cells from HEK293 cells that were stably transfected with a PIMT small interfering RNA expression vector. PIMT activities were significantly decreased in the PIMT knockdown cells, and analysis of the transfectants revealed that MEK and ERK were hyperactivated after cell stimulation with epidermal growth factor (EGF). These results indicate that the ability to repair L-isoaspartyl-(or D-aspartyl-) containing proteins is important for the maintenance of normal MEK-ERK signaling.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 127 (12), 1927-1936, 2007

    公益社団法人 日本薬学会

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