Premium
Heat shock protein 90 regulates stabilization rather than activation of soluble guanylate cyclase
Author(s) -
Nedvetsky Pavel I.,
Meurer Sabine,
Opitz Nils,
Nedvetskaya Tatiana Y.,
Müller Helmut,
Schmidt Harald H.H.W.
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.12.025
Subject(s) - hsp90 , mg132 , heme , gucy1a3 , chemistry , heat shock protein , nitric oxide , soluble guanylyl cyclase , guanylate cyclase , gucy1b3 , chaperone (clinical) , proteasome , microbiology and biotechnology , biochemistry , guanylate cyclase 2c , proteasome inhibitor , enzyme , biology , medicine , organic chemistry , pathology , gene
Endothelium‐derived nitric oxide (NO) activates the heterodimeric heme protein soluble guanylate cyclase (sGC) to form cGMP. In different disease states, sGC levels and activity are diminished possibly involving the sGC binding chaperone, heat shock protein 90 (hsp90). Here we show that prolonged hsp90 inhibition in different cell types reduces protein levels of both sGC subunits by about half, an effect that was prevented by the proteasome inhibitor MG132. Conversely, acute hsp90 inhibition affected neither basal nor NO‐stimulated sGC activity. Thus, hsp90 is a molecular stabilizer for sGC tonically preventing proteasomal degradation rather than having a role in short‐term activity regulation.