Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1760, Issue 11, Pages 1646-1656Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2006.08.026
Keywords
protein arginine methyltransferases; PRTMT7 alpha and beta; anticancer drug resistance
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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 PR-MT7 alpha 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. PRMT7 alpha 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. PRMT7 alpha and beta form homo- and hetero-dimers but differ by their sub-cellular localization and in vitro recognize different substrates. PRMT7 beta was only observed in Chinese hamster cells while mouse 10T1/2 fibroblasts only contain PRMT7 alpha. Surprisingly, in human cells the anti-PPMT7 antibody essentially recognized an similar to 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 PRMT7 alpha and detected a discrete number of proteins which methylation and/or expression are under the control of these enzymes. (c) 2006 Elsevier B.V. All rights reserved.
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