{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Soluble guanylate cyclase (sGC) is a heterodimeric receptor for nitric oxide (NO) that catalyzes the conversion of GTP to cyclic GMP (cGMP), a key second messenger mediating diverse cellular responses such as vascular smooth muscle relaxation, cell proliferation, neuroprotection, and apoptosis. The β‐subunit of sGC—commonly denoted as GUCY1B1 in earlier literature and now frequently referred to by its updated nomenclature—partners with the α‐subunit to form the catalytically active enzyme. Several studies have linked genetic variation and alternative splicing of sGC β‐subunit transcripts with human disease. For example, reduced expression or aberrant alternative splicing of the β‐subunit is associated with primary open‐angle glaucoma, underscoring a role in ocular blood flow regulation and neurodegeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In prostate cancer, oncogenic activation (e.g. via the ERG pathway) up‐regulates both sGC subunits, resulting in enhanced NO‐mediated cGMP synthesis and promoting cell proliferation, thereby identifying sGC as a potential therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, altered expression of multiple splice forms of the β‐subunit in malignant breast tissues suggests a loss of normal cGMP signaling that may contribute to tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, experimental models have demonstrated that silencing of the β‐subunit exacerbates cardiac dysfunction following ischemic injury, highlighting its cardioprotective function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Collectively, these findings emphasize that the GUCY1B1 (sGC β‐subunit) is central to NO–cGMP signaling, thereby regulating vascular tone, cellular proliferation, and neuroprotection, and that its dysregulation may contribute to the pathogenesis of glaucoma, cardiovascular disease, and various cancers.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emmanuel S Buys, Yu-Chieh Ko, Clemens Alt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soluble guanylate cyclase α1-deficient mice: a novel murine model for primary open angle glaucoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0060156"}], "href": "https://doi.org/10.1371/journal.pone.0060156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23527308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23527308"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Feng Zhou, Shuai Gao, Dong Han, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Differential expression of alternative transcripts of soluble guanylyl cyclase, GYCY1a3 and GUCY1b3 genes, in the malignant and benign breast tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nitric Oxide (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.niox.2018.12.009"}], "href": "https://doi.org/10.1016/j.niox.2018.12.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30597209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30597209"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaomin Wang, Wei Du, Meng Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The β subunit of soluble guanylyl cyclase GUCY1B3 exerts cardioprotective effects against ischemic injury via the PKCε/Akt pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.27479"}], "href": "https://doi.org/10.1002/jcb.27479"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30485489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30485489"}]}]}]}