Gene program-specific regulation of PGC-1α activity

Peroxisome proliferator-activated receptor gamma (PPAR gamma) coactivator 1 alpha (PGC-1 alpha) activation coordinates induction of the hepatic fasting response through coactivation of numerous transcription factors and gene programs. In the June 15, 2011, issue of Genes & Development, Lustig and colleagues (pp. 1232-1244) demonstrated that phosphorylation of PGC-1 alpha by the p70 ribosomal protein S6 kinase 1 (S6K1) specifically interfered with the interaction between PGC-1 alpha and HNF4 alpha in liver and blocked the coactivation of the gluconeogenic target genes. This demonstrates how independent fine-tuning of gene programs coregulated by the same coactivator can be obtained.