Characterization of prmt7α and β isozymes from Chinese hamster cells sensitive and resistant to topoisomerase II inhibitors
| Autor: | Axelle Renodon-Cornière, Marcin Feder, Laurent Gros, Janusz M. Bujnicki, Bruno Robert de Saint Vincent, Alain G. Jacquemin-Sablon |
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| Rok vydání: | 2006 |
| Předmět: |
Gene isoform
Protein-Arginine N-Methyltransferases Mutant Biophysics Methylation Biochemistry Isozyme Chinese hamster Mice chemistry.chemical_compound Cricetulus Species Specificity Cricetinae Tumor Cells Cultured Animals Humans Topoisomerase II Inhibitors Enzyme Inhibitors Molecular Biology biology Cell Cycle Alternative splicing Methyltransferases biology.organism_classification Molecular biology Isoenzymes DNA Topoisomerases Type II chemistry Dimerization DNA HeLa Cells |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - General Subjects. 1760:1646-1656 |
| ISSN: | 0304-4165 |
| DOI: | 10.1016/j.bbagen.2006.08.026 |
| Popis: | By selection of genetic suppressor elements (GSEs) conferring resistance to topoisomerase II inhibitors in Chinese hamster cells (DC-3F), we identified a gene encoding two proteins of 78 and 82 kDa which belong to the protein arginine methyltransferase (PRMT) family. Down-regulation of these enzymes (named PRMT7alpha and beta), either induced by an antisense GSE or as observed in the 9-OH-ellipticine (9-OH-E) resistant mutant DC-3F/9-OH-E, was responsible for cell resistance to various DNA damaging agents. Alternative splicing alterations in the 5'-terminal region and changes of the polyadenylation site of PRMT7 mRNAs were observed in these resistant mutant cells. PRMT7alpha and beta are isoforms of a highly conserved protein containing two copies of a module common to all PRMTs, comprising a Rossmann-fold domain and a beta-barrel domain. The C-terminal repeat appears to be degenerate and catalytically inactive. PRMT7alpha and beta form homo- and hetero-dimers but differ by their sub-cellular localization and in vitro recognize different substrates. PRMT7beta was only observed in Chinese hamster cells while mouse 10T1/2 fibroblasts only contain PRMT7alpha. Surprisingly, in human cells the anti-PRMT7 antibody essentially recognized an approximately 37 kDa peptide, which is not formed during extraction, and a faint band at 78 kDa. Analysis of in vitro and in vivo methylation patterns in cell lines under- or over-expressing PRMT7alpha and beta detected a discrete number of proteins which methylation and/or expression are under the control of these enzymes. |
| Databáze: | OpenAIRE |
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