{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSelenoprotein H (SELENOH) is a unique, small selenoprotein that functions as a nuclear/nucleolar oxidoreductase. Structural and sequence analyses reveal that it bears a thioredoxin‐like fold with a conserved CXXU motif—analogous to the CXXC motif in classical thioredoxins—endowing it with significant glutathione peroxidase activity. SELENOH contains distinct N‐terminal features, including an AT-hook DNA–binding motif and a nuclear localization signal that underlie its preferential nucleolar localization. Moreover, homology modeling and molecular dynamics studies demonstrate that the selenocysteine residue is critical for maintaining its active conformation and, consequently, its function in regulating redox balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its enzymatic antioxidant capacity, SELENOH plays an important regulatory role in cellular stress responses. In neuronal cells, overexpression of SELENOH protects against UVB-induced damage by preventing mitochondrial membrane depolarization and blocking the activation of the mitochondrial apoptotic pathway. This protective effect is associated with the up-regulation of mitochondrial biogenesis regulators (such as PGC-1α and NRF-1) and chaperone proteins, thereby enhancing mitochondrial function. Concurrently, SELENOH acts as a redox-responsive transcriptional regulator by binding to DNA sequences containing heat shock and stress response elements, which enhances the expression of enzymes involved in glutathione synthesis and phase II detoxification."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nLoss or down-regulation of SELENOH disrupts redox homeostasis and compromises genome maintenance. In cellular models, reduced SELENOH levels lead to enhanced oxidative stress, diminished glutathione content, activation of the ATM/p53 DNA damage response, and premature onset of cellular senescence. In vivo, SELENOH deficiency is associated with impaired redox balance, an inflammatory response, and an increased susceptibility to tumor formation, as evidenced in zebrafish and colorectal cancer cell models. These findings collectively underscore the role of SELENOH as a key regulator of cell cycle progression, stress response, and tumor suppression by preserving cellular redox balance and genomic integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sergey V Novoselov, Gregory V Kryukov, Xue-Ming Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selenoprotein H is a nucleolar thioredoxin-like protein with a unique expression pattern."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M701605200"}], "href": "https://doi.org/10.1074/jbc.M701605200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17337453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17337453"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sagar H Barage, Deepti D Deobagkar, Vijay B Baladhye "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of structural and functional role of selenocysteine in selenoprotein H and its impact on DNA binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Amino Acids (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00726-018-2543-5"}], "href": "https://doi.org/10.1007/s00726-018-2543-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29480333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29480333"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kamel E Ben Jilani, Jun Panee, Qingping He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of selenoprotein H reduces Ht22 neuronal cell death after UVB irradiation by preventing superoxide formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.3.198"}], "href": "https://doi.org/10.7150/ijbs.3.198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17389926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17389926"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jun Panee, Zoia R Stoytcheva, Wanyu Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selenoprotein H is a redox-sensing high mobility group family DNA-binding protein that up-regulates genes involved in glutathione synthesis and phase II detoxification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M702267200"}], "href": "https://doi.org/10.1074/jbc.M702267200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17526492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17526492"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Natalia Mendelev, Suresh L Mehta, Sam Witherspoon, et al. 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