{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:08:02Z","timestamp":1791896882582,"version":"4.3.4"},"reference-count":162,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T00:00:00Z","timestamp":1647043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56HL139564"],"award-info":[{"award-number":["R56HL139564"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL150049"],"award-info":[{"award-number":["R01HL150049"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The maturation of hemeprotein dictates that they incorporate heme and become active, but knowledge of this essential cellular process remains incomplete. Studies on chaperon Hsp90 has revealed that it drives functional heme maturation of inducible nitric oxide synthase (iNOS), soluble guanylate cyclase (sGC) hemoglobin (Hb) and myoglobin (Mb) along with other proteins including GAPDH, while globin heme maturations also need an active sGC. In all these cases, Hsp90 interacts with the heme-free or apo-protein and then drives the heme maturation by an ATP dependent process before dissociating from the heme-replete proteins, suggesting that it is a key player in such heme-insertion processes. As the studies on globin maturation also need an active sGC, it connects the globin maturation to the NO-sGC (Nitric oxide-sGC) signal pathway, thereby constituting a novel NO-sGC-Globin axis. Since many aggressive cancer cells make Hb\u03b2\/Mb to survive, the dependence of the globin maturation of cancer cells places the NO-sGC signal pathway in a new light for therapeutic intervention. Given the ATPase function of Hsp90 in heme-maturation of client hemeproteins, Hsp90 inhibitors often cause serious side effects and this can encourage the alternate use of sGC activators\/stimulators in combination with specific Hsp90 inhibitors for better therapeutic intervention.<\/jats:p>","DOI":"10.3390\/cells11060976","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T22:29:43Z","timestamp":1647210583000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Hsp90 in Human Diseases: Molecular Mechanisms to Therapeutic Approaches"],"prefix":"10.3390","volume":"11","author":[{"given":"Mamta P.","family":"Sumi","sequence":"first","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7498-1994","authenticated-orcid":false,"given":"Arnab","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s12192-012-0320-z","article-title":"Ferruccio Ritossa\u2019s scientific legacy 50 years after his discovery of the heat shock response: A new view of biology, a new society, and a new journal","volume":"17","author":"Santoro","year":"2012","journal-title":"Cell Stress Chaperones"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12111","DOI":"10.1016\/S0021-9258(19)38314-0","article-title":"Heat shock proteins","volume":"265","author":"Schlesinger","year":"1990","journal-title":"J. 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