Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5

Molecular and Cellular Biology
Rick B VegaTimothy A McKinsey

Abstract

A variety of stress signals stimulate cardiac myocytes to undergo hypertrophy. Persistent cardiac hypertrophy is associated with elevated risk for the development of heart failure. Recently, we showed that class II histone deacetylases (HDACs) suppress cardiac hypertrophy and that stress signals neutralize this repressive function by triggering phosphorylation- and CRM1-dependent nuclear export of these chromatin-modifying enzymes. However, the identities of cardiac HDAC kinases have remained unclear. Here, we demonstrate that signaling by protein kinase C (PKC) is sufficient and, in some cases, necessary to drive nuclear export of class II HDAC5 in cardiomyocytes. Inhibition of PKC prevents nucleocytoplasmic shuttling of HDAC5 in response to a subset of hypertrophic agonists. Moreover, a nonphosphorylatable HDAC5 mutant is refractory to PKC signaling and blocks cardiomyocyte hypertrophy mediated by pharmacological activators of PKC. We also demonstrate that protein kinase D (PKD), a downstream effector of PKC, directly phosphorylates HDAC5 and stimulates its nuclear export. These findings reveal a novel function for the PKC/PKD axis in coupling extracellular cues to chromatin modifications that control cellular growth, and the...Continue Reading

References

Aug 1, 1992·The American Journal of Physiology·S N AlloH E Morgan
Aug 1, 1990·Journal of Molecular and Cellular Cardiology·P M DunnmonK R Chien
Jan 10, 1997·The Journal of Biological Chemistry·K NishikawaL C Cantley
May 16, 1997·The Journal of Biological Chemistry·S Nishikawa, T Endo
Dec 31, 1997·The Journal of Clinical Investigation·J C BowmanP M Buttrick
Oct 9, 1998·The Journal of Biological Chemistry·T IglesiasE Rozengurt
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·C M GrozingerS L Schreiber
Sep 16, 1999·The EMBO Journal·E A MiskaT Kouzarides
Sep 18, 1999·Cell·K R Chien
Mar 29, 2000·Proceedings of the National Academy of Sciences of the United States of America·J LuE N Olson
May 17, 2000·The Journal of Clinical Investigation·R PassierE N Olson
Jun 9, 2000·Annual Review of Physiology·W R MacLellan, M D Schneider
Jun 28, 2000·Proceedings of the National Academy of Sciences of the United States of America·C M Grozinger, S L Schreiber
Dec 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·T A McKinseyE N Olson
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·S S Hook, A R Means
Apr 12, 2001·American Journal of Physiology. Heart and Circulatory Physiology·B B RomanP M Buttrick
Aug 4, 2001·Molecular and Cellular Biology·A H Wang, X J Yang
Aug 11, 2001·Science·T Jenuwein, C D Allis
Aug 18, 2001·Molecular and Cellular Biology·T A McKinseyE N Olson
Oct 5, 2001·The Journal of Biological Chemistry·H Y KaoS Khochbin
Feb 14, 2002·Trends in Biochemical Sciences·Timothy A McKinseyEric N Olson
Feb 14, 2002·Chemistry & Biology·Christina M Grozinger, Stuart L Schreiber
Apr 12, 2002·The International Journal of Biochemistry & Cell Biology·Johan Van LintJackie R Vandenheede
Nov 6, 2002·Journal of Biochemistry·Yasuhito Shirai, Naoaki Saito
Jan 14, 2003·Annual Review of Physiology·N Frey, E N Olson
Mar 19, 2003·Journal of Neurochemistry·Sangeeta ChawlaHilmar Bading
May 23, 2003·The Journal of Biological Chemistry·Christopher L AntosEric N Olson
Aug 2, 2003·Journal of Cellular Physiology·Osvaldo ReyEnrique Rozengurt
Feb 18, 2004·Nature Medicine·Julian C BrazJeffery D Molkentin
Feb 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Erik BushEric N Olson
Mar 26, 2004·Trends in Genetics : TIG·Timothy A McKinsey, Eric N Olson

❮ Previous
Next ❯

Citations

May 9, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Shin-ichi OkaJunichi Sadoshima
May 11, 2006·Current Heart Failure Reports·Risto Kerkela, Thomas Force
Jun 19, 2010·Journal of Cardiovascular Translational Research·Tetsuro AgoJunichi Sadoshima
Jun 19, 2010·Journal of Cardiovascular Translational Research·Shigeki MiyamotoJoan Heller Brown
Mar 3, 2011·Cell Death & Disease·R PaolettiM Bouché
Jun 17, 2008·Nature Chemical Biology·Jay W SchneiderJenny Hsieh
May 1, 2007·Nature Medicine·Rebecca BerdeauxMarc Montminy
Jul 24, 2007·Nature Reviews. Drug Discovery·Timothy A McKinsey, David A Kass
Aug 29, 2006·Nature Reviews. Molecular Cell Biology·Joerg Heineke, Jeffery D Molkentin
Feb 23, 2008·Nature Reviews. Molecular Cell Biology·Xiang-Jiao Yang, Edward Seto
May 25, 2010·Nature Structural & Molecular Biology·Catherine T Pawson, John D Scott
Feb 28, 2007·Cell Research·Paola GallinariChristian Steinkühler
Aug 19, 2007·Oncogene·M MartinF Dequiedt
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jens FielitzEric N Olson
May 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shusheng WangEric N Olson
Jan 31, 2009·Proceedings of the National Academy of Sciences of the United States of America·Johannes BacksEric N Olson
Aug 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Chang Hoon HaZheng Gen Jin
May 31, 2013·Proceedings of the National Academy of Sciences of the United States of America·Bradley S FergusonTimothy A McKinsey
Feb 24, 2010·The Journal of Biological Chemistry·Kun WangPei-Feng Li
Nov 3, 2010·The Journal of Biological Chemistry·Mariah H GoodallTerry B Rogers
Dec 16, 2010·The Journal of Biological Chemistry·Jianfen GuoSusan F Steinberg
Jan 9, 2013·The Journal of Biological Chemistry·Donald R WalkinshawXiang-Jiao Yang
Nov 26, 2008·The Journal of Biological Chemistry·Eric D JensenJennifer J Westendorf
Aug 16, 2008·The Journal of Biological Chemistry·Hector BiliranErkki Ruoslahti
Oct 3, 2008·The Journal of Biological Chemistry·Elizabeth R SharlowQ Jane Wang
Nov 26, 2008·The Journal of Biological Chemistry·Vitalyi O RybinSusan F Steinberg
Jun 24, 2008·The Journal of Biological Chemistry·R John Solaro
Nov 18, 2010·Molecular & Cellular Proteomics : MCP·Todd M GrecoIleana M Cristea
Aug 7, 2012·Molecular & Cellular Proteomics : MCP·Amanda J GuiseIleana M Cristea
Nov 7, 2012·The Journal of Experimental Medicine·Arne IttnerRomeo Ricci
Oct 21, 2005·Molecular Biology of the Cell·Timothy A McKinseyEric N Olson
Nov 11, 2005·Molecular Biology of the Cell·Fang LiuGary D Kao
Jul 18, 2008·Molecular Biology of the Cell·Carmen C SucharovTimothy A McKinsey
Jul 18, 2008·Molecular Biology of the Cell·Andrew J WilsonJohn M Mariadason
Jan 27, 2009·Cardiovascular Research·Suresh Selvaraj PalaniyandiDaria Mochly-Rosen
Feb 9, 2010·Molecular Human Reproduction·S K MunroA P Ponnampalam
Jul 23, 2013·Molecular Human Reproduction·Ching-Wen ChangHungwen Chen
Dec 19, 2007·Nucleic Acids Research·Cecilia AngelelliSusanna Molinari
Jul 3, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xiao PanJames J Pestka
Jun 10, 2010·Journal of Cardiovascular Pharmacology·Shikha MishraJoan Heller Brown

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Cardiomegaly

Cardiomegaly, known as an enlarged heart, is a multifactorial disease with different pathophysiological mechanisms. Hypertension, pregnancy, exercise-induced and idiopathic causes are some mechanisms of cardiomegaly. Discover the latest research of cardiomegaly here.