{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTXNDC17, also known as TRP14, is an evolutionarily conserved member of the thioredoxin protein family that exhibits unique redox activity. Unlike classical Trx1, TXNDC17 displays a dedicated disulfide reductase function with remarkable catalytic efficiency in reducing l‑cystine when coupled to Trx reductase 1, and it efficiently catalyzes S‑denitrosylation reactions that restore the activities of nitrosylated proteins. Detailed biochemical characterizations and high‐resolution structural studies have revealed that its atypical redox‐active motif and surface charge distribution not only stabilize the thiolate anion of its catalytic cysteine but also confer substrate specificity distinct from that of Trx1. These features underscore its key role in maintaining cellular thiol balance and reducing disulfide bonds in selected protein substrates."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its intrinsic reductase activity, TXNDC17 plays a pivotal role in redox‐dependent signaling. It modulates inflammatory and apoptotic responses by maintaining key signaling proteins such as the dynein light chain LC8 in a reduced state. Under pro‐oxidant conditions, LC8 can form disulfide‐linked homodimers that dissociate from its binding partner IκBα, thereby facilitating NF‑κB activation; however, TXNDC17 counteracts this effect by catalyzing the reduction of oxidized LC8. This activity is critical for tempering TNF‑α–induced signaling pathways, highlighting TXNDC17 as an important redox regulator in cellular stress responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTXNDC17 has also emerged as a clinically relevant molecule in cancer biology. In ovarian cancer, its high expression is linked to paclitaxel resistance via the upregulation of BECN1-mediated autophagy, contributing to poorer patient outcomes. Moreover, aberrant TXNDC17 expression has been identified in colorectal cancer tissues and plasma, suggesting its potential as an early diagnostic marker and therapeutic target. Together, these findings underline the multifaceted roles of TXNDC17 in both cellular redox homeostasis and oncogenic signaling, making it an attractive candidate for further investigation in disease contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Woojin Jeong, Hae Won Yoon, Seung-Rock Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of TRP14, a thioredoxin-related protein of 14 kDa. 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"}, {"type": "b", "children": [{"type": "t", "text": "Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1317320111"}], "href": "https://doi.org/10.1073/pnas.1317320111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24778250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24778250"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ajanta Chatterji, Rajib Sengupta "}, {"type": "b", "children": [{"type": "t", "text": "Cellular S-denitrosylases: Potential role and interplay of Thioredoxin, TRP14, and Glutaredoxin systems in thiol-dependent protein denitrosylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2020.105904"}], "href": "https://doi.org/10.1016/j.biocel.2020.105904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33359085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33359085"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Pablo Martí-Andrés, Isabela Finamor, Isabel Torres-Cuevas, et al. 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