First Author | Sun C | Year | 2014 |
Journal | Cell Rep | Volume | 9 |
Issue | 6 | Pages | 2250-62 |
PubMed ID | 25497092 | Mgi Jnum | J:222658 |
Mgi Id | MGI:5645184 | Doi | 10.1016/j.celrep.2014.11.029 |
Citation | Sun C, et al. (2014) PCAF improves glucose homeostasis by suppressing the gluconeogenic activity of PGC-1alpha. Cell Rep 9(6):2250-62 |
abstractText | PGC-1alpha plays a central role in hepatic gluconeogenesis and has been implicated in the onset of type 2 diabetes. Acetylation is an important posttranslational modification for regulating the transcriptional activity of PGC-1alpha. Here, we show that PCAF is a pivotal acetyltransferase for acetylating PGC-1alpha in both fasted and diabetic states. PCAF acetylates two lysine residues K328 and K450 in PGC-1alpha, which subsequently triggers its proteasomal degradation and suppresses its transcriptional activity. Adenoviral-mediated expression of PCAF in the obese mouse liver greatly represses gluconeogenic enzyme activation and glucose production and improves glucose homeostasis and insulin sensitivity. Moreover, liver-specific knockdown of PCAF stimulates PGC-1alpha activity, resulting in an increase in blood glucose and hepatic glucose output. Our results suggest that PCAF might be a potential pharmacological target for developing agents against metabolic disorders associated with hyperglycemia, such as obesity and diabetes. |