Accession Number:

ADA551301

Title:

Maintenance of Glucose Homeostasis Through Acetylation of the Metabolic Transcriptional Coactivator PGC1-alpha

Descriptive Note:

Final rept. 9 Jan 2006-8 Jan 2011

Corporate Author:

DANA-FARBER CANCER INST BOSTON MA

Personal Author(s):

Report Date:

2011-02-01

Pagination or Media Count:

103.0

Abstract:

We have tested the hypothesis that acetylation of PGC-1 by GCN5 and associated proteins control hepatic glucose production. Here, a summary of the accomplished tasks is provided. Task 1, a detailed analysis of the role of Pc3 and WDR18 on GCN5-mediated transcription on gluconeogenic genes has been performed. Task 2, we have confirmed that Pc3 and WDR18 are part of the PGC-1 GCN5 complex but are not required for its assembly. Task 3, we identified the major acetylation sites on PGC-1 that account for the pro-gluconeogenic effects. Task 4, we have identified the mechanisms whereby GCN5 suppress PGC-1 activity, in part through Pc3 and WDR18. Task 5, we have analyzed the suppressive effects of GCN5 on hepatic glucose metabolism. Task 6, we have identified that additional GCN5 interacting proteins including the Sirtuin 6 activate GCN5 and suppress hepatic glucose output. The final conclusions are that PGC-1 acetylation is a key chemical switch that in response to fedfasting controls liver metabolism.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research
  • Organic Chemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE