Protein methyltransferase 2 inhibits NF-kappaB function and promotes apoptosis.

Molecular and Cellular Biology
Lakshmanan GaneshGary J Nabel

Abstract

The protein arginine methyltransferases (PRMTs) include a family of proteins with related putative methyltransferase domains that modify chromatin and regulate cellular transcription. Although some family members, PRMT1 and PRMT4, have been implicated in transcriptional modulation or intracellular signaling, the roles of other PRMTs in diverse cellular processes have not been fully established. Here, we report that PRMT2 inhibits NF-kappaB-dependent transcription and promotes apoptosis. PRMT2 exerted this effect by blocking nuclear export of IkappaB-alpha through a leptomycin-sensitive pathway, increasing nuclear IkappaB-alpha and decreasing NF-kappaB DNA binding. The highly conserved S-adenosylmethionine-binding domain of PRMT2 mediated this effect. PRMT2 also rendered cells susceptible to apoptosis by cytokines or cytotoxic drugs, likely due to its effects on NF-kappaB. Mouse embryo fibroblasts from PRMT2 genetic knockouts showed elevated NF-kappaB activity and decreased susceptibility to apoptosis compared to wild-type or complemented cells. Taken together, these data suggest that PRMT2 inhibits cell activation and promotes programmed cell death through this NF-kappaB-dependent mechanism.

References

Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D M MarkovitzG J Nabel
Nov 15, 1995·Genes & Development·I M VermaS Miyamoto
Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·P J ChiaoI M Verma
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·K BrownU Siebenlist
Nov 1, 1996·Science·D J Van AntwerpI M Verma
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·M E GerritsenT Collins
Jul 1, 1997·Mammalian Genome : Official Journal of the International Mammalian Genome Society·N KatsanisE M Fisher
Oct 6, 1997·Science·B Ossareh-NazariC Dargemont
May 15, 1998·Trends in Biochemical Sciences·J M AlettaM J Ettinger
Sep 30, 1998·Progress in Nucleic Acid Research and Molecular Biology·J D Gary, S Clarke
Jun 26, 1999·Science·D ChenM R Stallcup
Feb 10, 2000·Annals of the New York Academy of Sciences·C DelaporteA Jacquemin-Sablon
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah
Jan 3, 2001·The Journal of Clinical Investigation·A S Baldwin
Mar 16, 2001·Current Opinion in Genetics & Development·M Merika, D Thanos
Sep 20, 2001·Genes & Development·N Silverman, T Maniatis
Dec 26, 2001·EMBO Reports·Uta-Maria BauerTony Kouzarides

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Citations

Jun 16, 2009·Human Genetics·David Patterson
Dec 14, 2012·Nature Reviews. Cancer·Yanzhong Yang, Mark T Bedford
Jun 21, 2011·Eukaryotic Cell·John C Fisk, Laurie K Read
Mar 29, 2012·Current Gerontology and Geriatrics Research·Donna M Wilcock
Jul 20, 2013·Journal of Neuroinflammation·Donna M Wilcock, W Sue T Griffin
Mar 24, 2007·Reproduction : the Official Journal of the Society for the Study of Fertility·Serge McGrawMarc-André Sirard
Oct 22, 2015·Journal of Medicinal Chemistry·Adriana GrozavBruno Therrien
Apr 7, 2016·Proceedings of the National Academy of Sciences of the United States of America·Anja ReintjesTaras Valovka
Dec 30, 2014·Carcinogenesis·Neelam MukherjeeRita Ghosh
May 25, 2012·Expert Opinion on Therapeutic Targets·Boksik Cha, Eek-Hoon Jho
Feb 18, 2015·Mutagenesis·Alan MorettinJocelyn Côté
Sep 30, 2014·Advances in Biological Regulation·Sanzida Jahan, James R Davie
Jan 20, 2009·Molecular Cell·Mark T Bedford, Steven G Clarke
Apr 18, 2006·Experimental Cell Research·Takanobu YoshimotoElizabeth G Nabel
Jan 4, 2017·Expert Review of Proteomics·Chao Peng, Catherine Cl Wong
Jan 7, 2017·Molecular Cell·Roméo S Blanc, Stéphane Richard
May 22, 2018·Expert Opinion on Therapeutic Targets·Emily SmithRobert A Baiocchi
Nov 16, 2010·FEBS Letters·Alessandra Di Lorenzo, Mark T Bedford
Aug 22, 2007·Journal of Cellular Physiology·Sharmistha Pal, Saïd Sif
Dec 12, 2019·Molecular Neurobiology·Alexandre Couto E SilvaHung Wen Lin
May 28, 2016·The Journal of Biological Chemistry·James B HayesDavid E Nelson
Oct 1, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emilie DalloneauYann Hérault
Mar 19, 2019·Acta Biochimica Et Biophysica Sinica·Yajun ChenJing Zhong
Oct 14, 2017·Nature Communications·Simona InfantinoDavid Tarlinton
Aug 9, 2020·Clinical Science·Chunyun Zhang, Shougang Zhuang
May 8, 2013·Glia·Aleksandra Ellert-MiklaszewskaBozena Kaminska
Sep 23, 2019·Methods : a Companion to Methods in Enzymology·Sinja RakowCaroline Bouchard
Jan 15, 2021·Cells·Jean-Paul BryantYeshavanth Kumar Banasavadi-Siddegowda
Aug 29, 2006·Biochemical Pharmacology·Wim Vanden BergheGuy Haegeman
Feb 20, 2020·Biochemical and Biophysical Research Communications·Hengli NiuLing Chen
Oct 17, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Junji ZhuWuhan Xiao

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