{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T12:56:09Z","timestamp":1773492969723,"version":"3.50.1"},"reference-count":80,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Telethon Foundation","award":["GGP20079"],"award-info":[{"award-number":["GGP20079"]}]},{"name":"Italian Telethon Foundation","award":["955534"],"award-info":[{"award-number":["955534"]}]},{"name":"European Cystic Fibrosis Society (ECFS) (Gerd D\u00f6ring Award 2022","award":["GGP20079"],"award-info":[{"award-number":["GGP20079"]}]},{"name":"European Cystic Fibrosis Society (ECFS) (Gerd D\u00f6ring Award 2022","award":["955534"],"award-info":[{"award-number":["955534"]}]},{"name":"Cystic Fibrosis Europe (CF Europe) (ECFS\/CF Europe Post-Doctoral Research Fellowship","award":["GGP20079"],"award-info":[{"award-number":["GGP20079"]}]},{"name":"Cystic Fibrosis Europe (CF Europe) (ECFS\/CF Europe Post-Doctoral Research Fellowship","award":["955534"],"award-info":[{"award-number":["955534"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["GGP20079"],"award-info":[{"award-number":["GGP20079"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["955534"],"award-info":[{"award-number":["955534"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Over the last fifteen years, with the approval of the first molecular treatments, a breakthrough era has begun for patients with cystic fibrosis (CF), the rare genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These molecules, known as CFTR modulators, have led to unprecedented improvements in the lung function and quality of life of most CF patients. However, the efficacy of these drugs is still suboptimal, and the clinical response is highly variable even among individuals bearing the same mutation. Furthermore, not all patients carrying rare CFTR mutations are eligible for CFTR modulator therapies, indicating the need for alternative and\/or add-on therapeutic approaches. Because the second messenger 3\u2032,5\u2032-cyclic adenosine monophosphate (cAMP) represents the primary trigger for CFTR activation and a major regulator of different steps of the life cycle of the channel, there is growing interest in devising ways to fine-tune the cAMP signaling pathway for therapeutic purposes. This review article summarizes current knowledge regarding the role of cAMP signalosomes, i.e., multiprotein complexes bringing together key enzymes of the cAMP pathway, in the regulation of CFTR function, and discusses how modulating this signaling cascade could be leveraged for therapeutic intervention in CF.<\/jats:p>","DOI":"10.3390\/ijms241310538","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T01:42:32Z","timestamp":1687743752000},"page":"10538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["It Takes Two to Tango! Protein\u2013Protein Interactions behind cAMP-Mediated CFTR Regulation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3039-4285","authenticated-orcid":false,"given":"Alessandra","family":"Murabito","sequence":"first","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center \u201cGuido Tarone\u201d, University of Torino, 10126 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6614-2597","authenticated-orcid":false,"given":"Janki","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center \u201cGuido Tarone\u201d, University of Torino, 10126 Torino, Italy"},{"name":"Kither Biotech S.r.l., 10126 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1193-5296","authenticated-orcid":false,"given":"Alessandra","family":"Ghigo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center \u201cGuido Tarone\u201d, University of Torino, 10126 Torino, Italy"},{"name":"Kither Biotech S.r.l., 10126 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/S0140-6736(20)32542-3","article-title":"Cystic fibrosis","volume":"397","author":"Shteinberg","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The future of cystic fibrosis care: A global perspective","volume":"8","author":"Bell","year":"2020","journal-title":"Lancet Respir. 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