The laforin/malin E3-ubiquitin ligase complex ubiquitinates pyruvate kinase M1/M2.

Q2 Biochemistry, Genetics and Molecular Biology

BMC Biochemistry Pub Date : 2015-10-23 DOI:10.1186/s12858-015-0053-6

Rosa Viana, Pablo Lujan, Pascual Sanz

{"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":"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.","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}

引用次数: 18

Abstract

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.

Abstract Image

查看原文本刊更多论文

laforin/malin E3-泛素连接酶复合物泛素化丙酮酸激酶 M1/M2。

背景：拉弗拉病（LD，OMIM 254780）是一种致命的神经退行性疾病，主要由两个基因突变引起：EPM2A编码双重特异性磷酸酶laforin，EPM2B编码E3-泛素连接酶malin。尽管人们已经知道，laforin 和 malin 可能会形成一个功能性复合物，但这种病理现象的潜在分子机制还远未被人们所了解：为了获得有关 laforin/malin 复合物底物的信息，我们进行了酵母底物诱捕筛选，该筛选最初是为了确定蛋白酪氨酸磷酸酶的底物：结果：我们发现丙酮酸激酶的两种肌肉异构体（PKM1和PKM2）是拉弗林的新型相互作用伙伴：我们提出的证据表明，laforin/malin 复合物能够与 PKM1 和 PKM2 相互作用并使其泛素化。这种翻译后修饰虽然不会影响 PKM1 的催化活性，但会损害 PKM2 的核定位。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

BMC Biochemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

4.80

自引率

0.00%

发文量

审稿时长

3 months

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.