Maintenance of Glucose Homeostasis through Acetylation of the Metabolic Transcriptional Coactivator PGC1-alpha
Abstract
The main purpose of this proposal is to test the hypothesis that acetylation of PGC-1alpha by GCN5 and associated proteins, Pc3 and WDR18, controls hepatic glucose production. The major findings of this Research Technical Report are in tasks 2, 4, 5 and 6. In task 2, we have further confirmed that Pc3 and WDR18 are part of the PGC-1alpha/GCN5 complex but are not required for its assembly. In task 4, we have analyzed the effects of Pc3 and WDR18 on gluconeogenic/glycolytic genes. In task 5, we have analyzed the negative effects of GCN5 on hepatic glucose metabolism. In Task 6, we have generated GCN5 and PGC-1alpha shRNA adenoviruses to knock-down these genes in liver. Overall, the experiments reported indicate that PGC-1alpha acetylation is a key chemical switch that in response to fed/fasting controls liver metabolism. We will continue to complete the proposed tasks to understand how PCC-1alpha acetylation controls hepatic glucose production through the GCN5 complex.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2009
- Accession Number
- ADA503185
Entities
People
- Pere Puigserver i Burguera
Organizations
- Dana–Farber Cancer Institute