The arginine methyltransferase PRMT2 binds RB and regulates E2F function

Experimental Cell Research
Takanobu YoshimotoElizabeth G Nabel

Abstract

The retinoblastoma gene product (RB) is an important regulator of E2F activity. RB recruits a number of proteins, including HDACs, SWI/SNF complex, lysine methyl transferase (SUV39H1) and DNA methyltransferase (DNMT1), all of which negatively regulate E2F activity with RB. Here, we show that RB interacts with PRMT2, a member of the protein arginine methyltransferase family, to regulate E2F activity. PRMT2 directly bound and interacted with RB through its AdoMet binding domain, in contrast to other PRMT proteins, including PRMT1, PRMT3 and PRMT4. In reporter assays, PRMT2 repressed E2F1 transcriptional activity in an RB-dependent manner. PRMT2 formed a ternary complex with E2F1 in the presence of RB. To further explore the role of endogenous PRMT2 in the regulation of E2F activity, the PRMT2 gene was ablated in mice by gene targeting. Compared with PRMT2(+/+) mouse embryonic fibroblasts (MEFs), PRMT2(-/-) MEFs demonstrated increased E2F activity and early S phase entry following release of serum starvation. Vascular injury to PRMT2(-/-) arteries results in a hyperplastic response, consistent with increased G1-S phase progression. Taken together, these findings demonstrate a novel mechanism for the regulation of E2F activity by a...Continue Reading

References

Dec 1, 1994·Molecular and Cellular Biology·B Shan, W H Lee
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·X Q QinP D Adams
Mar 26, 1993·Science·M Ohtsubo, J M Roberts
Jul 1, 1997·Mammalian Genome : Official Journal of the International Mammalian Genome Society·N KatsanisE M Fisher
May 15, 1998·Trends in Biochemical Sciences·J M AlettaM J Ettinger
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·A M PierceD G Johnson
Aug 8, 1998·Genes & Development·N Dyson
Jun 26, 1999·Science·D ChenM R Stallcup
Oct 6, 2000·Genes & Development·J W Harbour, D C Dean
Dec 2, 2000·Nature Structural Biology·V H WeissJ M Hogle
Aug 3, 2001·Nature·S J NielsenT Kouzarides
Oct 5, 2001·Molecular Cell·A DahiyaD C Dean
Dec 26, 2001·EMBO Reports·Uta-Maria BauerTony Kouzarides
Feb 2, 2002·Nature Reviews. Molecular Cell Biology·Jeffrey M Trimarchi, Jacqueline A Lees
Jun 1, 2002·The Journal of Biological Chemistry·Chao QiYi-Jun Zhu
Aug 3, 2004·The Journal of Clinical Investigation·Manfred BoehmElizabeth G Nabel
May 2, 2006·Molecular and Cellular Biology·Lakshmanan GaneshGary J Nabel

❮ Previous
Next ❯

Citations

Nov 20, 2008·Reproduction : the Official Journal of the Society for the Study of Fertility·Raúl Fernández-GonzálezAlfonso Gutiérrez-Adán
Sep 28, 2010·The Journal of Biological Chemistry·Louis A SaddicJulien Sage
Jun 16, 2009·Human Genetics·David Patterson
Nov 16, 2010·FEBS Letters·Alessandra Di Lorenzo, Mark T Bedford
Aug 1, 2009·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Thomas B NicholsonStéphane Richard
Dec 17, 2014·Journal of Experimental & Clinical Cancer Research : CR·Rouzbeh DaylamiRichard J Bold
May 25, 2012·Expert Opinion on Therapeutic Targets·Boksik Cha, Eek-Hoon Jho
Feb 18, 2015·Mutagenesis·Alan MorettinJocelyn Côté
Aug 20, 2015·PloS One·Maryem A HusseinMichael J Garabedian
Mar 24, 2018·Cell Division·Anita E Raposo, Sabine C Piller
May 22, 2018·Expert Opinion on Therapeutic Targets·Emily SmithRobert A Baiocchi
Jun 21, 2011·Eukaryotic Cell·John C Fisk, Laurie K Read
Aug 22, 2007·Journal of Cellular Physiology·Sharmistha Pal, Saïd Sif
Jan 9, 2019·Journal of Molecular Endocrinology·Shu-Ching M WangGeorge E O Muscat
Dec 14, 2012·Nature Reviews. Cancer·Yanzhong Yang, Mark T Bedford
Apr 19, 2007·The Journal of Biological Chemistry·Rafal SwierczMark T Bedford
Aug 25, 2016·Oncotarget·Coralie PoulardMuriel Le Romancer
May 14, 2016·Molecular Medicine Reports·Lei LiRan Huo
Oct 1, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emilie DalloneauYann Hérault
Dec 7, 2007·Journal of Cell Science·Mark T Bedford
May 8, 2020·Current Protein & Peptide Science·Ayad A Al-HamashiRong Huang
Oct 17, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Junji ZhuWuhan Xiao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.