Abstract
The eukaryotic cell has evolved a variety of stress responses against external stimuli, such as innate immunity, the formation of stress granules (SGs), and autophagy. We previously demonstrated that the innate immune adaptor IFN-β promoter stimulator 1 (IPS-1) plays an essential role in the formation of dsRNA-induced SGs, indicating a connection between SG formation and innate immunity. In this study, it was further demonstrated that melanoma differentiation-associated gene 5 (MDA5), an innate immune sensor, is involved in SG formation induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial protonophore. MDA5 knockdown had no significant impact on the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) triggered by CCCP, and MDA5 itself was not recruited to SGs, suggesting that the regulation of MDA5 in the SG response occurs downstream of eIF2α. Furthermore, the depletion of MDA5 or G3BP1 led to reduced autophagy in CCCP-stimulated cells, implying that the regulatory effect of MDA5 with respect to autophagy depends on its role in SG formation. This study uncovered an unexpected role of the innate immune protein MDA5 in SG formation and autophagy triggered by the protonophore CCCP, furthe...Continue Reading
References
Jan 21, 1997·Biochimica Et Biophysica Acta·J W ParkH R Kim
Dec 30, 1999·The Journal of Cell Biology·N L KedershaP Anderson
Mar 29, 2000·Proceedings of the National Academy of Sciences of the United States of America·I E GallouziJ A Steitz
Dec 7, 2000·Molecular Cell·H P HardingD Ron
Nov 19, 2002·FEBS Letters·Laura E McLeod, Christopher G Proud
Mar 19, 2003·The Journal of Cell Biology·Helene TourrièreJamal Tazi
Jun 23, 2004·Nature Immunology·Mitsutoshi YoneyamaTakashi Fujita
Mar 12, 2005·Pigment Cell Research·Andrea M Hall, Seth J Orlow
Jul 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Marie-Eve BordeleauJerry Pelletier
Aug 16, 2005·Genes, Brain, and Behavior·L N AntarG J Bassell
Aug 30, 2005·Cell·Rashu B SethZhijian J Chen
Jul 11, 2006·Nature·Etienne MeylanMichael Karin
Jul 28, 2006·Molecular Biology of the Cell·Rachid MazrouiJerry Pelletier
Sep 5, 2006·The Journal of Biological Chemistry·Yongjun DangJun O Liu
Nov 15, 2006·The Journal of Cell Biology·Nadine StöhrStefan Hüttelmaier
Oct 16, 2008·The Journal of Biological Chemistry·Katerina ChalupníkováYoshikuni Nagamine
Jan 13, 2010·Molecular Cell·J Ross Buchan, Roy Parker
Nov 29, 2011·Biochemical and Biophysical Research Communications·Kyum-Yil KwonOok Joon Yoo
Mar 29, 2013·Journal of Virology·Martijn A LangereisFrank J van Kuppeveld
Jun 21, 2013·Journal of Virology·Chen Seng NgTakashi Fujita
Jun 26, 2013·Cell·J Ross BuchanRoy Parker
Sep 14, 2013·Trends in Biochemical Sciences·Nancy KedershaPaul Anderson
Mar 19, 2014·Cell·Lisa Vincenz, F Ulrich Hartl
Mar 25, 2014·Journal of Cell Science·Peifen ZhangPing Zhang
Aug 21, 2014·Frontiers in Microbiology·Jia-Rong JhengJim-Tong Horng