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[The role of isomerized protein repair enzyme, PIMT, in cellular functions]

[The role of isomerized protein repair enzyme, PIMT, in cellular functions] Research Abstract Details 

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  • [The role of isomerized protein repair enzyme, PIMT, in cellular functions] Abstract Text:

    takemitsu furuchiTakemitsu Furuchi,hiroshi hommaHiroshi Homma,takemitsu furuchiTakemitsu Furuchi,hiroshi hommaHiroshi Homma,takemitsu furuchiTakemitsu Furuchi,hiroshi hommaHiroshi Homma,

    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 alpha-carboxyl group of an L-isoaspartyl (or the beta-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.

    [The role of isomerized protein repair enzyme, PIMT, in cellular functions] Publishing Authors By Initials

    t furuchiT Furuchi,h hommaH Homma,t furuchiT Furuchi,h hommaH Homma,t furuchiT Furuchi,h hommaH Homma,

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    [The role of isomerized protein repair enzyme, PIMT, in cellular functions] Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Yakugaku zasshi : Journal of the Pharmaceutical So

    VOLUME: 127

    Page Numbers: 1927-36

    Journal Abbreviation: Yakugaku Zasshi

    ISSN: 0031-6903

    DAY: 6

    MONTH: Dec

    YEAR: 2007

    [The role of isomerized protein repair enzyme, PIMT, in cellular functions] Information

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    LANGUAGE: jpn

    NlmUniqueID: 413613

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    Grant and Affiliation Information for [The role of isomerized protein repair enzyme, PIMT, in cellular functions]

    AFFILIATION: Sch. of Pharmaceut. Sci., Kitasato Univ, 5-9-1 Shirogane, Minato-ku, Tokyo 108-8641, Japan.

    Country: Japan

    Japan Research PublicationJapan Research Publication

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    MEDLINETA: Yakugaku Zasshi

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