Novel mechanism of cyclic nucleotide crosstalk mediated by PKG-dependent proteasomal degradation of the Hsp90 client protein phosphodiesterase 3A.

ABSTRACT: Endothelial cAMP-specific phosphodiesterase PDE3A is one of the major negative regulators of the endothelial barrier function in acute lung injury models. However, the mechanisms underlying its regulation still need to be fully resolved. We show here that the PDE3A is a newly described client of the molecular chaperone heat shock protein 90 (hsp90). In endothelial cells (ECs), hsp90 inhibition by geldanamycin (GA) led to a disruption of the hsp90/PDE3A complex, followed by a significant decrease in PDE3A protein levels. The decrease in PDE3A protein levels was ubiquitin-proteasome-dependent and required the activity of the E3 ubiquitin ligase C terminus of Hsc70-interacting protein. GA treatment also enhanced the association of PDE3A with hsp70, which partially prevented PDE3A degradation.

SUBMITTER: Zemskov EA 

PROVIDER: S-EPMC11497409 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature