{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOLA1 is a highly conserved Obg‐like ATPase that has emerged as a multifunctional regulator of cellular homeostasis, proliferation, and genomic stability. Initial characterization of OLA1 (originally identified as Gbp45) underscored its essential role in cell proliferation and survival in relation to mitochondrial function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cancer cells, OLA1 has been shown to influence multiple aspects of tumor biology. It interacts with the tumor suppressor complex BRCA1/BARD1, contributing to centrosome regulation and ensuring proper centriole duplication"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", while its dysregulation may lead to centrosome amplification."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, altered OLA1 expression impacts cell adhesion and spreading"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", promotes epithelial‐to‐mesenchymal transition (EMT) through modulation of signaling pathways such as GSK3β/Snail/E‐cadherin"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", and is associated with aggressive clinical features in breast, colorectal, gastric, and other cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": " OLA1 also exhibits a dual role in cancer, as its proper function is critical for maintaining centrosomal homeostasis—a role further implicated in oral cancer metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel to these roles in cell proliferation and oncogenesis, OLA1 acts as a pivotal mediator of cellular stress responses and translational control. It functions as a negative regulator of the antioxidant defense system by suppressing nontranscriptional activation of cellular antioxidant machinery"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and it stabilizes key chaperones such as HSP70 by interfering with its ubiquitination."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Beyond protein quality control, OLA1 modulates protein synthesis by binding to eukaryotic initiation factor 2 (eIF2) and hydrolyzing GTP to interfere with ternary complex formation, thereby promoting the integrated stress response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Its role in coupling redox signals to metabolic gene transcription is critical for maintaining mitochondrial bioenergetics and cardiovascular function—as evidenced by phosphorylation‐dependent nuclear translocation that activates nuclear–encoded mitochondrial genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " These diverse regulatory functions are integrated within broader proteostatic networks as reviewed in recent summaries of OLA1 structure and activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies have highlighted context‐specific roles for OLA1. In T cells, for example, the HIV p17 protein hijacks OLA1 function by disrupting its complex with glycogen synthase kinase‐3β (GSK3β), an event that suppresses autophagy and facilitates aberrant cell proliferation under nutrient stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Collectively, these findings reveal that OLA1 is a critical molecular switch integrating stress responses, translational control, and cytoskeletal as well as metabolic regulation—with significant implications for tumor progression, cardiovascular pathology, and viral pathogenesis.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yukimi Kira, Manabu Nishikawa "}, {"type": "b", "children": [{"type": "t", "text": "The identification and characterization of a new GTP-binding protein (Gbp45) involved in cell proliferation and death related to mitochondrial function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2478/s11658-008-0023-8"}], "href": "https://doi.org/10.2478/s11658-008-0023-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18536999"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18536999"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ayako Matsuzawa, Shin-Ichiro Kanno, Masahiro Nakayama, et al. 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