| First Author | Kise Y | Year | 2006 |
| Journal | Biochem Biophys Res Commun | Volume | 351 |
| Issue | 1 | Pages | 78-84 |
| PubMed ID | 17054904 | Mgi Jnum | J:115277 |
| Mgi Id | MGI:3691263 | Doi | 10.1016/j.bbrc.2006.10.036 |
| Citation | Kise Y, et al. (2006) Fused kinase is stabilized by Cdc37/Hsp90 and enhances Gli protein levels. Biochem Biophys Res Commun 351(1):78-84 |
| abstractText | Serine/threonine kinase Fused (Fu) is an essential component of Hedgehog (Hh) signaling in Drosophila, but the biochemical functions of Fu remain unclear. Here, we have investigated proteins co-precipitated with mammalian Fu and identified a kinase-specific chaperone complex, Cdc37/Hsp90, as a novel-binding partner of Fu. Inhibition of Hsp90 function by geldanamycin (GA) induces rapid degradation of Fu through a ubiquitin-proteasome pathway. We next show that co-expression of Fu with transcription factors Gli1 and Gli2 significantly increases their protein levels and luciferase reporter activities, which are blocked by GA. These increases can be ascribed to Fu-mediated stabilization of Gli because co-expression of Fu prolongs half-life of Gli1 and reduces polyubiquitination of Gli1. Finally, we show that GA inhibits proliferation of PC3, a Hh signaling-activated prostate cancer cell line. This growth inhibition is partially rescued by expression of ectopic Gli1, suggesting that Fu may contribute to enhance Hh signaling activity in cancer cells. |
