| http://purl.uniprot.org/citations/27617292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27617292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27617292 | http://www.w3.org/2000/01/rdf-schema#comment | "The intronic GGGGCC hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) is a prevalent genetic abnormality identified in both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Smith-Magenis syndrome chromosomal region candidate gene 8 (SMCR8) is a protein with unclear functions. We report that C9ORF72 is a component of a multiprotein complex containing SMCR8, WDR41, and ATG101 (an important regulator of autophagy). The C9ORF72 complex displays guanosine triphosphatase (GTPase) activity and acts as a guanosine diphosphate-guanosine 5'-triphosphate (GDP-GTP) exchange factor (GEF) for RAB39B. We created Smcr8 knockout mice and found that Smcr8 mutant cells exhibit impaired autophagy induction, which is similarly observed in C9orf72 knockdown cells. Mechanistically, SMCR8/C9ORF72 interacts with the key autophagy initiation ULK1 complex and regulates expression and activity of ULK1. The complex has an additional role in regulating later stages of autophagy. Whereas autophagic flux is enhanced in C9orf72 knockdown cells, depletion of Smcr8 results in a reduced flux with an abnormal expression of lysosomal enzymes. Thus, C9ORF72 and SMCR8 have similar functions in modulating autophagy induction by regulating ULK1 and play distinct roles in regulating autophagic flux."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.org/dc/terms/identifier | "doi:10.1126/sciadv.1601167"xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.org/dc/terms/identifier | "doi:10.1126/sciadv.1601167"xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Liang C."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Liang C."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Yang M."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Yang M."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Swaminathan K."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Swaminathan K."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Lai F."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Lai F."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Shiekhattar R."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Shiekhattar R."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Chen J.F."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Chen J.F."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Herrlinger S."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/author | "Herrlinger S."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/name | "Sci. Adv."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/name | "Sci. Adv."xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/pages | "E1601167"xsd:string |
| http://purl.uniprot.org/citations/27617292 | http://purl.uniprot.org/core/pages | "E1601167"xsd:string |