{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNME9, also known as Txl‐2, is a bifunctional protein composed of an N‐terminal thioredoxin domain and a C‐terminal nucleoside-diphosphate kinase (NDPK) domain. This arrangement allows it to potentially integrate redox regulation with nucleotide homeostasis. Notably, alternative splicing generates distinct isoforms – one, in particular, the Delta 5 variant, exhibits a strong intrinsic microtubule binding capacity, suggesting a novel role in modulating microtubule physiology in structures such as airway epithelial cilia and spermatid flagella."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nProteomics studies of lung tissues, although not exclusively centered on NME9, have underscored the importance of proteins with redox and kinase functions in pulmonary biology. These findings support the idea that proteins like NME9 may contribute to maintaining cellular organization and function in complex tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of colon cancer, NME9 isoforms display differential biological activities. One study demonstrated that distinct splicing variants of Txl‐2 influence key steps of tumor progression, including cell invasion and metastasis, suggesting that NME9 may help drive the dissemination of colon cancer cells. Complementary research on the most abundant isoform, Txl‐2b, revealed that its overexpression promotes cell proliferation, accelerates the cell cycle, and confers resistance to apoptosis through the activation of NF‑κB signaling, thereby contributing to tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, studies of related thioredoxin family enzymes in lymphomas have highlighted the broader significance of redox-regulatory proteins in cancer biology. Expression patterns of these antioxidant enzymes correlate with clinical outcomes in diffuse large B-cell lymphoma, suggesting that the mechanistic insights illuminated by research on NME9 might reflect wider roles for thioredoxin-related proteins in modulating cellular stress responses and tumor biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christine M Sadek, Alberto Jiménez, Anastasios E Damdimopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of human thioredoxin-like 2. A novel microtubule-binding thioredoxin expressed predominantly in the cilia of lung airway epithelium and spermatid manchette and axoneme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M300369200"}], "href": "https://doi.org/10.1074/jbc.M300369200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12569107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12569107"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eun Joo Lee, Kwang Ho In, Je Hyeong Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic analysis in lung tissue of smokers and COPD patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1378/chest.08-1583"}], "href": "https://doi.org/10.1378/chest.08-1583"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18753468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18753468"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuanyuan Lu, Xiaodi Zhao, Kai Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin-like protein 2 is overexpressed in colon cancer and promotes cancer cell metastasis by interaction with ran."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2012.4736"}], "href": "https://doi.org/10.1089/ars.2012.4736"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23311631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23311631"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuanyuan Lu, Xiaodi Zhao, Guanhong Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin-like protein 2b facilitates colon cancer cell proliferation and inhibits apoptosis via NF-κB pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2014.12.048"}], "href": "https://doi.org/10.1016/j.canlet.2014.12.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25555669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25555669"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Mikko C Chan, Janette Savela, Riina K Ollikainen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testis-Specific Thioredoxins TXNDC2, TXNDC3, and TXNDC6 Are Expressed in Both Testicular and Systemic DLBCL and Correlate with Clinical Disease Presentation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oxid Med Cell Longev (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/8026941"}], "href": "https://doi.org/10.1155/2021/8026941"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33603952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33603952"}]}]}]}