| First Author | Oishi Y | Year | 2008 |
| Journal | Nat Med | Volume | 14 |
| Issue | 6 | Pages | 656-66 |
| PubMed ID | 18500350 | Mgi Jnum | J:137059 |
| Mgi Id | MGI:3797697 | Doi | 10.1038/nm1756 |
| Citation | Oishi Y, et al. (2008) SUMOylation of Kruppel-like transcription factor 5 acts as a molecular switch in transcriptional programs of lipid metabolism involving PPAR-delta. Nat Med 14(6):656-66 |
| abstractText | Obesity and metabolic syndrome are increasingly recognized as major risk factors for cardiovascular disease. Herein we show that Kruppel-like transcription factor 5 (KLF5) is a crucial regulator of energy metabolism. Klf5(+/-) mice were resistant to high fat-induced obesity, hypercholesterolemia and glucose intolerance, despite consuming more food than wild-type mice. This may in part reflect their enhanced energy expenditure. Expression of the genes involved in lipid oxidation and energy uncoupling, including those encoding carnitine-palmitoyl transferase-1b (Cpt1b) and uncoupling proteins 2 and 3 (Ucp2 and Ucp3), was upregulated in the soleus muscles of Klf5(+/-) mice. Under basal conditions, KLF5 modified with small ubiquitin-related modifier (SUMO) proteins was associated with transcriptionally repressive regulatory complexes containing unliganded peroxisome proliferator-activated receptor-delta (PPAR-delta) and co-repressors and thus inhibited Cpt1b, Ucp2 and Ucp3 expression. Upon agonist stimulation of PPAR-delta, KLF5 was deSUMOylated, and became associated with transcriptional activation complexes containing both the liganded PPAR-delta and CREB binding protein (CBP). This activation complex increased the expression of Cpt1b, Ucp2 and Ucp3. Thus, SUMOylation seems to be a molecular switch affecting function of KLF5 and the transcriptional regulatory programs governing lipid metabolism. |
