| Autor: |
Gros L; CNRS FRE2618, Laboratoire de Pharmacologie des Agents Anticancéreux, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux, France., Renodon-Cornière A, de Saint Vincent BR, Feder M, Bujnicki JM, Jacquemin-Sablon A |
| Jazyk: |
angličtina |
| Zdroj: |
Biochimica et biophysica acta [Biochim Biophys Acta] 2006 Nov; Vol. 1760 (11), pp. 1646-56. Date of Electronic Publication: 2006 Sep 14. |
| DOI: |
10.1016/j.bbagen.2006.08.026 |
| Abstrakt: |
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: |
MEDLINE |
| Externí odkaz: |
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