http://purl.uniprot.org/citations/29634390 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/29634390 | http://www.w3.org/2000/01/rdf-schema#comment | "Post-translational modifications of autophagy-related (ATG) genes are necessary to modulate their functions. However, ATG protein methylation and its physiological role have not yet been elucidated. The methylation of non-histone proteins by SETD7, a SET domain-containing lysine methyltransferase, is a novel regulatory mechanism to control cell protein function in response to various cellular stresses. Here we present evidence that the precise activity of ATG16L1 protein in hypoxia/reoxygenation (H/R)-treated cardiomyocytes is regulated by a balanced methylation and phosphorylation switch. We first show that H/R promotes autophagy and decreases SETD7 expression, whereas autophagy inhibition by 3-MA increases SETD7 level in cardiomyocytes, implying a tight correlation between autophagy and SETD7. Then we demonstrate that SETD7 methylates ATG16L1 at lysine 151 while KDM1A/LSD1 (lysine demethylase 1A) removes this methyl mark. Furthermore, we validate that this methylation at lysine 151 impairs the binding of ATG16L1 to the ATG12-ATG5 conjugate, leading to inhibition of autophagy and increased apoptosis in H/R-treated cardiomyocytes. However, the cardiomyocytes with shRNA-knocked down SETD7 or inhibition of SETD7 activity by a small molecule chemical, display increased autophagy and decreased apoptosis following H/R treatment. Additionally, methylation at lysine 151 inhibits phosphorylation of ATG16L1 at S139 by CSNK2 which was previously shown to be critical for autophagy maintenance, and vice versa. Together, our findings define a novel modification of ATG16L1 and highlight the importance of an ATG16L1 phosphorylation-methylation switch in determining the fate of H/R-treated cardiomyocytes."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.org/dc/terms/identifier | "doi:10.1080/15548627.2017.1389357"xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Feng X."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Liu Q."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Luo Y."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Lin F."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Zhang Z."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Song H."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Wang L."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Xu X."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Wu Q."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Zhang M."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Ding X."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Jin X."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Yu T."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/author | "Liang G."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/name | "Autophagy"xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/pages | "825-844"xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/title | "Crosstalk between lysine methylation and phosphorylation of ATG16L1 dictates the apoptosis of hypoxia/reoxygenation-induced cardiomyocytes."xsd:string |
http://purl.uniprot.org/citations/29634390 | http://purl.uniprot.org/core/volume | "14"xsd:string |
http://purl.uniprot.org/citations/29634390 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29634390 |
http://purl.uniprot.org/citations/29634390 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29634390 |
http://purl.uniprot.org/uniprot/#_D9N2U2-mappedCitation-29634390 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29634390 |