TY  - GEN
AB  - Fibroblast 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.
AD  - Oregon Health and Science University
AU  - Laederich, Melanie
DA  - 2011
DO  - 10.6083/M4RF5S10
DO  - DOI
ID  - 620
KW  - Fibroblast Growth Factors
KW  - HSP90 Heat-Shock Proteins
KW  - Cell Cycle Proteins
KW  - Achondroplasia
KW  - Neoplasms
KW  - Receptor, Fibroblast Growth Factor, Type 3
KW  - Heat-Shock Proteins
KW  - fgfr3
KW  - cancer
KW  - cdc37
L1  - https://digitalcollections.ohsu.edu/record/620/files/621_etd.pdf
L2  - https://digitalcollections.ohsu.edu/record/620/files/621_etd.pdf
L4  - https://digitalcollections.ohsu.edu/record/620/files/621_etd.pdf
LK  - https://digitalcollections.ohsu.edu/record/620/files/621_etd.pdf
N2  - Fibroblast 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.
PB  - Oregon Health and Science University
PY  - 2011
T1  - Defining the role of HSP90 in the stability of FGFR3 and as a drug target for the treatment of skeletal  diseases and cancer
TI  - Defining the role of HSP90 in the stability of FGFR3 and as a drug target for the treatment of skeletal  diseases and cancer
UR  - https://digitalcollections.ohsu.edu/record/620/files/621_etd.pdf
Y1  - 2011
ER  -