{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSeveral studies have revealed that the NOSTRIN protein (and its mouse orthologue mNOSTRIN/mDaIP2) functions not only in the cytoplasm but also in the nucleus as a transcriptional regulator. In mouse embryonic carcinoma cells, NOSTRIN was originally identified as mDaIP2, a protein containing an N‐terminal FCH domain and a C‐terminal SH3 domain that interacts with mDab2. Notably, NOSTRIN can bind directly to its own promoter via a putative bZIP motif and leucine zipper, thereby repressing its transcription in a negative feedback loop during cell differentiation (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional work has established that regulation of endothelial nitric oxide synthase (eNOS) is multifaceted. While PECAM-1 plays a role in modulating basal eNOS activity in response to mechanical shear stress (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]), NOSTRIN itself acts as a critical modulator of eNOS function. By sequestering eNOS, NOSTRIN effectively diminishes nitric oxide (NO) production and, independent of direct eNOS catalytic activity, contributes to changes in the transcriptional profile of endothelial cells that impact proliferation, invasion, adhesion, and capillary tube formation (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, in vivo studies underscore a developmental and angiogenic role for NOSTRIN. In zebrafish and murine models, NOSTRIN is essential for proper vascular formation: it facilitates endothelial tip cell migration and filopodia extension through the assembly of a signaling complex that includes FGFR1, Rac1, and Sos1, thereby promoting fibroblast growth factor 2 (FGF2)-dependent Rac1 activation and angiogenesis. In parallel, its impact on endothelial function extends to pathological settings, where altered NOSTRIN expression and consequent deviations in eNOS activity contribute to endothelial dysfunction (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]).\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Young-Joon Choi, Si-Young Cho, Hyung-Wook Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and characterization of mouse disabled 2 interacting protein 2, a mouse orthologue of human NOSTRIN."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2004.11.079"}], "href": "https://doi.org/10.1016/j.bbrc.2004.11.079"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15596140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15596140"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hyung-Wook Kim, Young-Joon Choi, Jung-Ah Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mouse disabled 2 interacting protein 2 functions as a transcriptional repressor through direct binding onto its own promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.08.262"}], "href": "https://doi.org/10.1016/j.bbrc.2005.08.262"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16171775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16171775"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Seong-Ho Bae, Young-Joon Choi, Kyung-hyun Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the cis-element and bZIP DNA binding motifs for the autogenous negative control of mouse NOSTRIN."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2013.12.066"}], "href": "https://doi.org/10.1016/j.bbrc.2013.12.066"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24361894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24361894"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Margaret E McCormick, Reema Goel, David Fulton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Platelet-endothelial cell adhesion molecule-1 regulates endothelial NO synthase activity and localization through signal transducers and activators of transcription 3-dependent NOSTRIN expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.110.216200"}], "href": "https://doi.org/10.1161/ATVBAHA.110.216200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21183735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21183735"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shreeta Chakraborty, Rupasri Ain "}, {"type": "b", "children": [{"type": "t", "text": "Nitric-oxide synthase trafficking inducer is a pleiotropic regulator of endothelial cell function and signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.742627"}], "href": "https://doi.org/10.1074/jbc.M116.742627"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28235804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28235804"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Igor Kovacevic, Jiong Hu, Ann Siehoff-Icking, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The F-BAR protein NOSTRIN participates in FGF signal transduction and vascular development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2012.176"}], "href": "https://doi.org/10.1038/emboj.2012.176"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22751148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22751148"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Igor Kovacevic, Miriam Müller, Baktybek Kojonazarov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The F-BAR Protein NOSTRIN Dictates the Localization of the Muscarinic M3 Receptor and Regulates Cardiovascular Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.115.306187"}], "href": "https://doi.org/10.1161/CIRCRESAHA.115.306187"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26169369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26169369"}]}]}]}