| http://purl.uniprot.org/citations/30771306 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30771306 | http://www.w3.org/2000/01/rdf-schema#comment | "Cardiac functionality is dependent on a balanced protein turnover. Accordingly, regulated protein decay is critical to maintain cardiac function. Here we demonstrate that deficiency of SPRED2, an intracellular repressor of ERK-MAPK signaling markedly expressed in human heart, resulted in impaired autophagy, heart failure, and shortened lifespan. SPRED2-/- mice showed cardiomyocyte hypertrophy, cardiac fibrosis, impaired electrical excitability, and severe arrhythmias. Mechanistically, cardiomyocyte dysfunction resulted from ERK hyperactivation and dysregulated autophagy, observed as accumulation of vesicles, vacuolar structures, and degenerated mitochondria. The diminished autophagic flux in SPRED2-/- hearts was reflected by a reduced LC3-II/LC3-I ratio and by decreased Atg7, Atg4B and Atg16L expression. Furthermore, the autophagosomal adaptors p62/SQSTM1 and NBR1 and lysosomal Cathepsin D accumulated in SPRED2-/- hearts. In wild-type hearts, SPRED2 interacted physically with p62/SQSTM1, NBR1, and Cathepsin D, indicating that SPRED2 is required for autophagolysosome formation in regular autophagy. Restored inhibition of MAPK signaling by selumetinib led to an increase in autophagic flux in vivo. Therefore, our study identifies SPRED2 as a novel, indispensable regulator of cardiac autophagy. Vice versa, SPRED2 deficiency impairs autophagy, leading to cardiac dysfunction and life-threatening arrhythmias."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.yjmcc.2019.01.023"xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Kuhn M."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Werner F."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Unger A."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Benz P.M."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Schuh K."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Linke W.A."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Wagner H."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Frantz S."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Ullrich M."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Baba H.A."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Assmus B."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Abesser M."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Umbenhauer S."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Erkens R."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Arias-Loza A.P."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Augustin A.M."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Habich H."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/author | "Martin Machado J."xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/name | "J Mol Cell Cardiol"xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/pages | "13-26"xsd:string |
| http://purl.uniprot.org/citations/30771306 | http://purl.uniprot.org/core/title | "SPRED2 deficiency elicits cardiac arrhythmias and premature death via impaired autophagy."xsd:string |