{"title":"laforin/malin E3-泛素连接酶复合物泛素化丙酮酸激酶 M1/M2。","authors":"Rosa Viana, Pablo Lujan, Pascual Sanz","doi":"10.1186/s12858-015-0053-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lafora disease (LD, OMIM 254780) is a fatal neurodegenerative disorder produced mainly by mutations in two genes: EPM2A, encoding the dual specificity phosphatase laforin, and EPM2B, encoding the E3-ubiquitin ligase malin. Although it is known that laforin and malin may form a functional complex, the underlying molecular mechanisms of this pathology are still far from being understood.</p><p><strong>Methods: </strong>In order to gain information about the substrates of the laforin/malin complex, we have carried out a yeast substrate-trapping screening, originally designed to identify substrates of protein tyrosine phosphatases.</p><p><strong>Results: </strong>Our results identify the two muscular isoforms of pyruvate kinase (PKM1 and PKM2) as novel interaction partners of laforin.</p><p><strong>Conclusions: </strong>We present evidence indicating that the laforin/malin complex is able to interact with and ubiquitinate both PKM1 and PKM2. This post-translational modification, although it does not affect the catalytic activity of PKM1, it impairs the nuclear localization of PKM2.</p>","PeriodicalId":9113,"journal":{"name":"BMC Biochemistry","volume":"16 ","pages":"24"},"PeriodicalIF":0.0000,"publicationDate":"2015-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12858-015-0053-6","citationCount":"18","resultStr":"{\"title\":\"The laforin/malin E3-ubiquitin ligase complex ubiquitinates pyruvate kinase M1/M2.\",\"authors\":\"Rosa Viana, Pablo Lujan, Pascual Sanz\",\"doi\":\"10.1186/s12858-015-0053-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Lafora disease (LD, OMIM 254780) is a fatal neurodegenerative disorder produced mainly by mutations in two genes: EPM2A, encoding the dual specificity phosphatase laforin, and EPM2B, encoding the E3-ubiquitin ligase malin. Although it is known that laforin and malin may form a functional complex, the underlying molecular mechanisms of this pathology are still far from being understood.</p><p><strong>Methods: </strong>In order to gain information about the substrates of the laforin/malin complex, we have carried out a yeast substrate-trapping screening, originally designed to identify substrates of protein tyrosine phosphatases.</p><p><strong>Results: </strong>Our results identify the two muscular isoforms of pyruvate kinase (PKM1 and PKM2) as novel interaction partners of laforin.</p><p><strong>Conclusions: </strong>We present evidence indicating that the laforin/malin complex is able to interact with and ubiquitinate both PKM1 and PKM2. This post-translational modification, although it does not affect the catalytic activity of PKM1, it impairs the nuclear localization of PKM2.</p>\",\"PeriodicalId\":9113,\"journal\":{\"name\":\"BMC Biochemistry\",\"volume\":\"16 \",\"pages\":\"24\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2015-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1186/s12858-015-0053-6\",\"citationCount\":\"18\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Biochemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s12858-015-0053-6\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Biochemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s12858-015-0053-6","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
The laforin/malin E3-ubiquitin ligase complex ubiquitinates pyruvate kinase M1/M2.
Background: Lafora disease (LD, OMIM 254780) is a fatal neurodegenerative disorder produced mainly by mutations in two genes: EPM2A, encoding the dual specificity phosphatase laforin, and EPM2B, encoding the E3-ubiquitin ligase malin. Although it is known that laforin and malin may form a functional complex, the underlying molecular mechanisms of this pathology are still far from being understood.
Methods: In order to gain information about the substrates of the laforin/malin complex, we have carried out a yeast substrate-trapping screening, originally designed to identify substrates of protein tyrosine phosphatases.
Results: Our results identify the two muscular isoforms of pyruvate kinase (PKM1 and PKM2) as novel interaction partners of laforin.
Conclusions: We present evidence indicating that the laforin/malin complex is able to interact with and ubiquitinate both PKM1 and PKM2. This post-translational modification, although it does not affect the catalytic activity of PKM1, it impairs the nuclear localization of PKM2.
期刊介绍：
BMC Biochemistry is an open access journal publishing original peer-reviewed research articles in all aspects of biochemical processes, including the structure, function and dynamics of metabolic pathways, supramolecular complexes, enzymes, proteins, nucleic acids and small molecular components of organelles, cells and tissues. BMC Biochemistry (ISSN 1471-2091) is indexed/tracked/covered by PubMed, MEDLINE, BIOSIS, CAS, EMBASE, Scopus, Zoological Record, Thomson Reuters (ISI) and Google Scholar.
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