000000620 001__ 620 000000620 005__ 20260108120113.0 000000620 0247_ $$2DOI$$a10.6083/M4RF5S10 000000620 037__ $$aETD 000000620 245__ $$aDefining the role of HSP90 in the stability of FGFR3 and as a drug target for the treatment of skeletal diseases and cancer 000000620 260__ $$bOregon Health and Science University 000000620 269__ $$a2011 000000620 336__ $$aDissertation 000000620 502__ $$bPh.D. 000000620 502__ $$gCell & Developmental Biology (sunsetting) 000000620 520__ $$aFibroblast growth factor receptor 3 (FGFR3) regulates growth and differentiation, and its aberrant activation drives skeletal disorders and cancers. This work demonstrates that FGFR3 is inherently unstable and requires Hsp90 chaperone complexes for stability. Using biochemical analyses, we show that Hsp90 inhibition with small molecules (e.g., 17-AAG) induces FGFR3 ubiquitination and degradation. Other chaperone components, including Hsp70, Cdc37, and CHIP, also interact with FGFR3, suggesting additional therapeutic targets. These findings establish Hsp90 as a critical regulator of FGFR3 and support exploring Hsp90 inhibitors in FGFR3-driven cancers, while further studies are needed to assess their potential in skeletal diseases. 000000620 540__ $$fCC BY 000000620 542__ $$fIn copyright - single owner 000000620 650__ $$aFibroblast Growth Factors$$019019 000000620 650__ $$aHSP90 Heat-Shock Proteins$$031138 000000620 650__ $$aCell Cycle Proteins$$031101 000000620 650__ $$aAchondroplasia$$014134 000000620 650__ $$aNeoplasms$$022758 000000620 650__ $$aReceptor, Fibroblast Growth Factor, Type 3$$036871 000000620 650__ $$aHeat-Shock Proteins$$019966 000000620 6531_ $$afgfr3 000000620 6531_ $$acancer 000000620 6531_ $$acdc37 000000620 691__ $$aSchool of Medicine$$041369 000000620 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399 000000620 7001_ $$aLaederich, Melanie$$uOregon Health and Science University$$041354 000000620 8564_ $$9d2357895-b164-4bde-8ee4-38326e310568$$s2027221$$uhttps://digitalcollections.ohsu.edu/record/620/files/621_etd.pdf$$ePublic$$2c62ebc5aefc8d38d0ade3d3adf25aa0e$$31 000000620 905__ $$a/rest/prod/m3/26/m1/74/m326m174z 000000620 909CO $$ooai:digitalcollections.ohsu.edu:620$$pstudent-work 000000620 980__ $$aTheses and Dissertations