| http://purl.uniprot.org/citations/34267188 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34267188 | http://www.w3.org/2000/01/rdf-schema#comment | "Alcohol-related liver disease (ALD), a condition caused by alcohol overconsumption, occurs in three stages of liver injury including steatosis, hepatitis, and cirrhosis. DEP domain-containing protein 5 (DEPDC5), a component of GAP activities towards Rags 1 (GATOR1) complex, is a repressor of amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. In the current study, we found that aberrant activation of mTORC1 was likely attributed to the reduction of DEPDC5 in the livers of ethanol-fed mice or ALD patients. To further define the in vivo role of DEPDC5 in ALD development, we generated Depdc5 hepatocyte-specific knockout mouse model (Depdc5-LKO) in which mTORC1 pathway was constitutively activated through loss of the inhibitory effect of GATOR1. Hepatic Depdc5 ablation leads to mild hepatomegaly and liver injury and protects against diet-induced liver steatosis. In contrast, ethanol-fed Depdc5-LKO mice developed severe hepatic steatosis and inflammation. Pharmacological intervention with Torin 1 suppressed mTORC1 activity and remarkably ameliorated ethanol-induced hepatic steatosis and inflammation in both control and Depdc5-LKO mice. The pathological effect of sustained mTORC1 activity in ALD may be attributed to the suppression of peroxisome proliferator activated receptor α (PPARα), the master regulator of fatty acid oxidation in hepatocytes, because fenofibrate (PPARα agonist) treatment reverses ethanol-induced liver steatosis and inflammation in Depdc5-LKO mice. These findings provide novel insights into the in vivo role of hepatic DEPDC5 in the development of ALD."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41419-021-03980-6"xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Cao X."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Ma J."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Sun Z."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Zhang X."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Xu L."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Xiong X."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Yang C."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Hou G."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Zhang X.'"xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Xin Y."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/author | "Dong X.C."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/name | "Cell Death Dis"xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/pages | "710"xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/title | "Depdc5 deficiency exacerbates alcohol-induced hepatic steatosis via suppression of PPARalpha pathway."xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://purl.uniprot.org/core/volume | "12"xsd:string |
| http://purl.uniprot.org/citations/34267188 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34267188 |
| http://purl.uniprot.org/citations/34267188 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34267188 |
| http://purl.uniprot.org/uniprot/#_D3Z7M7-mappedCitation-34267188 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34267188 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YU49-mappedCitation-34267188 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34267188 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YV31-mappedCitation-34267188 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34267188 |
| http://purl.uniprot.org/uniprot/#_P61460-mappedCitation-34267188 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34267188 |