The Role of Heat Shock Protein-90 in the Pathogenesis of Birt-Hogg-Dube and Tuberous Sclerosis Complex Syndromes

Birt-Hogg-Dube (BHD) and tuberous sclerosis (TS) syndromes share many clinical features. These two diseases display distinct histologic subtypes of renal tumors: chromophobe renal cell carcinoma and renal angiomyolipoma, respectively. Early work suggested a role for mTOR dysregulation in the pathogenesis of these two diseases, however their detailed molecular link remains elusive. Interestingly, a growing number of case reports describe renal angiomyolipoma in BHD patients, suggesting a common molecular origin. The BHD-associated proteins FNIP1/2 and the TS protein Tsc1 were recently identified as regulators of the molecular chaperone Hsp90. Dysregulation of Hsp90 activity has previously been reported to support tumorigenesis, providing a potential explanation for the overlapping phenotypic manifestations in these two hereditary syndromes. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

Birt-Hogg-Dubé (BHD) and tuberous sclerosis (TS) syndromes share clinical features with distinct histologic subtypes of renal tumors. Dysregulation of mTOR and Hsp90 may play a role in the pathogenesis of these diseases, suggesting a common molecular origin and potential explanation for overlapping phenotypic manifestations. Further studies are needed to elucidate the detailed molecular link between these hereditary syndromes.