{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ASB10 is a gene encoding a protein that functions as an E3 ubiquitin ligase, thereby playing a key role in regulating protein turnover through the ubiquitin‐mediated degradation pathways. In ocular tissues—particularly in the trabecular meshwork, retinal ganglion cells, and ciliary body—ASB10 is abundantly expressed and localizes to distinct intracellular vesicular structures that are involved in the proteasomal and autophagy–lysosomal degradation systems. Functional studies show that alterations in ASB10 (including splice‐altering synonymous variants or amino acid changes that potentially destabilize its ankyrin repeat regions) can affect the homeostasis and turnover of proteins within these cells. Disruption of ASB10 expression has been linked to a reduction in aqueous humor outflow facility, thereby implicating it in glaucoma pathogenesis. In one set of studies, molecular and cell‐biological analyses demonstrated that ASB10 interacts with proteasomal components and chaperone proteins such as HSP70, suggesting that it contributes to the proper clearance of proteins through both the proteasome and autophagic pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, while associations between ASB10 variants and sporadic primary open‐angle glaucoma have been observed in some populations, other investigations indicate that non‐synonymous mutations in ASB10 do not account for classic Mendelian forms of the disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In an entirely different context, ASB10 has also been shown to function under the control of estrogen receptor–α in triple‐negative breast cancer, where it mediates the ubiquitination and resultant degradation of tumor endothelial marker 8 (TEM8), thereby influencing both cancer stem cell properties and neovasculogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, these studies collectively underscore that ASB10 acts as a critical regulator of protein quality control and turnover. By modulating proteasomal and autophagic pathways in ocular cells, ASB10 contributes to the maintenance of trabecular meshwork function and intraocular pressure regulation, whereas in other tissues its E3 ligase activity influences different cellular processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francesca Pasutto, Kate E Keller, Nicole Weisschuh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in ASB10 are associated with open-angle glaucoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddr572"}], "href": "https://doi.org/10.1093/hmg/ddr572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22156576"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22156576"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kate E Keller, Yong-Feng Yang, Ying Ying Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ankyrin repeat and suppressor of cytokine signaling box containing protein-10 is associated with ubiquitin-mediated degradation pathways in trabecular meshwork cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2013)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23901248"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23901248"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shazia Micheal, Humaira Ayub, Farrah Islam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in the ASB10 Gene Are Associated with Primary Open Angle Glaucoma."}]}, {"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.0145005"}], "href": "https://doi.org/10.1371/journal.pone.0145005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26713451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26713451"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "John H Fingert, Ben R Roos, Frances Solivan-Timpe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of ASB10 variants in open angle glaucoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds288"}], "href": "https://doi.org/10.1093/hmg/dds288"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22798626"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22798626"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jiahui Xu, Xiaoli Yang, Qiaodan Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-24703-7"}], "href": "https://doi.org/10.1038/s41467-021-24703-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34285210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34285210"}]}]}]}