PRMT5 is required for cell-cycle progression and p53 tumor suppressor function
Open Access
- 15 June 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 37 (15), 4965-4976
- https://doi.org/10.1093/nar/gkp516
Abstract
Protein arginine methyltransferases (PRMTs) mediate the transfer of methyl groups to arginines in proteins involved in signal transduction, transcriptional regulation and RNA processing. Tumor suppressor p53 coordinates crucial cellular processes, including cell-cycle arrest and DNA repair, in response to stress signals. Post-translational modifications and interactions with co-factors are important to regulate p53 transcriptional activity. To explore whether PRMTs modulate p53 function, we generated multiple cell lines in which PRMT1, CARM1 and PRMT5 are inducibly knocked down. Here, we showed that PRMT5, but not PRMT1 or CARM1, is essential for cell proliferation and PRMT5 deficiency triggers cell-cycle arrest in G1. In addition, PRMT5 is required for p53 expression and induction of p53 targets MDM2 and p21 upon DNA damage. Importantly, we established that PRMT5 knockdown prevents p53 protein synthesis. Furthermore, we found that PRMT5 regulates the expression of translation initiation factor eIF4E and growth suppression mediated upon PRMT5 knockdown is independent of p53 but is dependent on eIF4E. Taken together, we uncovered that arginine methyltransferase PRMT5 is a major pro-survival factor regulating eIF4E expression and p53 translation.Keywords
This publication has 39 references indexed in Scilit:
- Mdm2 Regulates p53 mRNA Translation through Inhibitory Interactions with Ribosomal Protein L26Molecular Cell, 2008
- Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteinsThe Journal of cell biology, 2007
- Modulation of p53 Function by SET8-Mediated Methylation at Lysine 382Molecular Cell, 2007
- Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphomaThe EMBO Journal, 2007
- The Lysine-specific Demethylase 1 Is Required for Cell Proliferation in Both p53-dependent and -independent MannersPublished by Elsevier BV ,2007
- The Protein Arginine Methyltransferase Prmt5 Is Required for Myogenesis because It Facilitates ATP-Dependent Chromatin RemodelingMolecular and Cellular Biology, 2007
- p53 modulation of the DNA damage responseJournal of Cellular Biochemistry, 2006
- Post-translational modification of p53 in tumorigenesisNature Reviews Cancer, 2004
- The Activation Domains, the Proline-rich Domain, and the C-terminal Basic Domain in p53 Are Necessary for Acetylation of Histones on the Proximal p21 Promoter and Interaction with p300/CREB-binding ProteinPublished by Elsevier BV ,2003
- Regulation of Transcription by a Protein MethyltransferaseScience, 1999