Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 32, Pages 12998-13003Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1205854109
Keywords
NO-dependent; cGMP-dependent; vasorelaxation
Categories
Funding
- National Institutes of Health [GM51491, HL076491]
Ask authors/readers for more resources
Heme insertion is key during maturation of soluble guanylyl cyclase (sGC) because it enables sGC to recognize NO and transduce its multiple biological effects. Although sGC is often associated with the 90-kDa heat shock protein (hsp90) in cells, the implications are unclear. The present study reveals that hsp90 is required to drive heme insertion into sGC and complete its maturation. We used a mammalian cell culture approach and followed heme insertion into transiently and endogenously expressed heme-free sGC. We used pharmacological hsp90 inhibitors, an ATP-ase inactive hsp90 mutant, and heme-dependent or heme-independent sGC activators as tools to decipher the role of hsp90. Our findings suggest that hsp90 complexes with apo-sGC, drives heme insertion through its inherent ATPase activity, and then dissociates from the mature, heme-replete sGC. Together, this improves our understanding of sGC maturation and reveals a unique means to control sGC activity in cells, and it has important implications for hsp90 inhibitor-based cancer therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available