title: Differential regulation of SC1/PRDM4 and PRMT5 mediated protein arginine methylation by the nerve growth factor and the epidermal growth factor in PC12 cells.
abstract: During neuronal development, the neuroepithelial stem cells (NSCs) initially undergo proliferative divisions, later switching to neurogenic ones whereby one NSC and a post-mitotic neuron are generated. We recently showed that a member of the PRDM family of transcriptional regulators, PRDM4/SC1, recruits a type II protein arginine methyltransferase, PRMT5, to maintain the "stem-like" cellular state of the embryonic mouse cortical NSCs. However, little is known about the regulation of activity of this complex under proliferation- or differentiation-inducing growth conditions. In the present work I investigate the regulation of SC1/PRMT5-mediated methylation activity in PC12 cells treated with EGF or NGF. I present evidence that NGF down-regulates SC1/PRMT5 methyltransferase (MTase) activity and that the reduction in SC1/PRMT5 MTase activity occurs mainly in the nucleus. I suggest that high levels of SC1/PRMT5 activity are associated with the proliferative state of the cells.
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London, WC1E 6BT, United Kingdom. a.chittka@ucl.ac.uk
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chittka
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D008745:Methylation; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D011496:Protein Methyltransferases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C121661:Prdm4 protein, rat; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D001120:Arginine; D011496:Protein Methyltransferases
keywords: (H)MTase; (histone) methyltransferase; EGF; Histone arginine methylation; NGF; NSC; PC12 cells; PRDM; PRDM4; PRMT; PRMT5; SC1; Schwann cell factor 1; epidermal growth factor; nerve growth factor; neural stem cells; positive regulatory domain protein; protein arginine methyltransferase