{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGamma‐tubulin 1 (TUBG1) is a critical structural and functional component of the γ‐tubulin ring complex (γ‐TuRC), which serves as the template for microtubule nucleation and is essential for proper centrosome organization and spindle formation. Structural studies have revealed that TUBG1 adopts a curved conformation and laterally associates with other γ‐tubulin molecules to form a template that supports the addition of α/β‐tubulin dimers, thereby driving microtubule polymerization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRegulation of TUBG1 function is achieved through a broad array of interacting partners and post‐translational modifications. Adaptor proteins (such as NEDD1/GCP‐WD) and kinases including Cdk1, Plk1, and GSK‐3β modulate the centrosomal recruitment and phosphorylation state of TUBG1 or its associated complex proteins, thereby influencing microtubule nucleation dynamics. Moreover, ubiquitin ligases such as the CUL4 complex and tumor suppressors like APC target TUBG1 for polyubiquitination and controlled proteolysis, while chaperonins such as CCT facilitate the remodeling of misfolded γ‐tubulin aggregates. Collectively, these regulatory events, which also involve other microtubule‐nucleating factors (e.g. GCP5) and anchoring proteins (e.g. Gravin), fine‐tune the assembly and stabilization of the microtubule network."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDeregulation of TUBG1 activity has significant clinical implications. Aberrant expression levels, mislocalization and epigenetic changes in the TUBG1 gene have been linked to a variety of malignancies including gliomas, breast, lung, and liver cancers, while de novo heterozygous mutations in TUBG1 are associated with tubulinopathies characterized by cortical malformations, microcephaly, epilepsy and motor impairments. In addition, emerging evidence supports that TUBG1 influences actin dynamics and participates in the DNA damage response—further highlighting its multifaceted roles in cell division and genomic stability. These findings indicate that both quantitative and qualitative alterations in TUBG1 function contribute to tumorigenesis and neurodevelopmental disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hector Aldaz, Luke M Rice, Tim Stearns, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insights into microtubule nucleation from the crystal structure of human gamma-tubulin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature03586"}], "href": "https://doi.org/10.1038/nature03586"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15917813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15917813"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "A S Zeiger, B E Layton "}, {"type": "b", "children": [{"type": "t", "text": "Molecular modeling of the axial and circumferential elastic moduli of tubulin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biophys J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1529/biophysj.108.131359"}], "href": "https://doi.org/10.1529/biophysj.108.131359"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18621829"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18621829"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiaoyan Zhang, Qiang Chen, Jia Feng, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Nek9 phosphorylation of NEDD1/GCP-WD contributes to Plk1 control of γ-tubulin recruitment to the mitotic centrosome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2012.06.027"}], "href": "https://doi.org/10.1016/j.cub.2012.06.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22818914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22818914"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nanae Izumi, Katsumi Fumoto, Shunsuke Izumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GSK-3beta regulates proper mitotic spindle formation in cooperation with a component of the gamma-tubulin ring complex, GCP5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M710282200"}], "href": "https://doi.org/10.1074/jbc.M710282200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18316369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18316369"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "María Alvarado-Kristensson, María Josefa Rodríguez, Virginia Silió, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "APC functions at the centrosome to stimulate microtubule growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2015.10.028"}], "href": "https://doi.org/10.1016/j.biocel.2015.10.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26556314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26556314"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Luis Pouchucq, Pablo Lobos-Ruiz, Gissela Araya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The chaperonin CCT promotes the formation of fibrillar aggregates of γ-tubulin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Proteins Proteom (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbapap.2018.01.007"}], "href": "https://doi.org/10.1016/j.bbapap.2018.01.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29339327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29339327"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Ella Fung, Carmen Richter, Hong-Bin Yang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Case reports: novel TUBG1 mutations with milder neurodevelopmental presentations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12881-019-0827-6"}], "href": "https://doi.org/10.1186/s12881-019-0827-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31151415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31151415"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Paula J Bucko, Irvin Garcia, Ridhima Manocha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gravin-associated kinase signaling networks coordinate γ-tubulin organization at mitotic spindle poles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.014791"}], "href": "https://doi.org/10.1074/jbc.RA120.014791"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32732289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32732289"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Darina Malycheva, Maria Alvarado-Kristensson "}, {"type": "b", "children": [{"type": "t", "text": "Centrosome Movements Are TUBG1-Dependent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms241713154"}], "href": "https://doi.org/10.3390/ijms241713154"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37685969"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37685969"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Christos D Katsetos, Eduarda Dráberová, Barbora Smejkalová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Class III beta-tubulin and gamma-tubulin are co-expressed and form complexes in human glioblastoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11064-007-9321-1"}], "href": "https://doi.org/10.1007/s11064-007-9321-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17406983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17406983"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Thomas Hubert, Sofie Perdu, Joël Vandekerckhove, et al. "}, {"type": "b", "children": [{"type": "t", "text": "γ-Tubulin localizes at actin-based membrane protrusions and inhibits formation of stress-fibers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2011.04.007"}], "href": "https://doi.org/10.1016/j.bbrc.2011.04.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21473851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21473851"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Xingjuan Shi, Xiaoou Sun, Min Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CEP70 protein interacts with γ-tubulin to localize at the centrosome and is critical for mitotic spindle assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.252262"}], "href": "https://doi.org/10.1074/jbc.M111.252262"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21795687"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21795687"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Thomas Hubert, Joël Vandekerckhove, Jan Gettemans "}, {"type": "b", "children": [{"type": "t", "text": "Cdk1 and BRCA1 target γ-tubulin to microtubule domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2011.09.064"}], "href": "https://doi.org/10.1016/j.bbrc.2011.09.064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21951856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21951856"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Ignacio Blanco, Karoline Kuchenbaecker, Daniel Cuadras, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0120020"}], "href": "https://doi.org/10.1371/journal.pone.0120020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25830658"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25830658"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Eduarda Dráberová, Vadym Sulimenko, Stanislav Vinopal, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Tubulinopathies continued: refining the phenotypic spectrum associated with variants in TUBG1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41431-018-0146-y"}], "href": "https://doi.org/10.1038/s41431-018-0146-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29706637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29706637"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Nicoletta F Maounis, Eduarda Dráberová, Nikos Trakas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of γ-tubulin in non-small cell lung cancer and effect on patient survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histol Histopathol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14670/HH-18-027"}], "href": "https://doi.org/10.14670/HH-18-027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30010174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30010174"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Zi-Jian Wang, Zhi-Zheng Dai, Mei-Zhen Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of TUBG1 expression promotes hepatocellular carcinoma development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Oncol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12032-023-01966-2"}], "href": "https://doi.org/10.1007/s12032-023-01966-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36792863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36792863"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yan Zhang, Zhen-Zhen Wang, An-Qi Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatobiliary Pancreat Dis Int (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.hbpd.2023.09.004"}], "href": "https://doi.org/10.1016/j.hbpd.2023.09.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37806848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37806848"}]}]}]}