{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence indicates that MIR8063 may serve as an important modulator within cellular stress‐response pathways. In particular, studies of endoplasmic reticulum (ER)–resident transcription factors—such as Luman/CREB3 and its interacting partner LRF, which promotes Luman degradation—underscore a regulatory network that governs the unfolded protein response (UPR) and related stress‐signaling cascades. These findings suggest that MIR8063 could interface with the UPR machinery to help fine‐tune cellular adaptation to ER stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, regulatory proteins studied in diverse cell types—including sLZIP, which functions as a corepressor modulating PPARγ activity to balance adipogenesis against osteogenesis, and factors that impact myogenesis and uterine decidualization—converge on pathways that determine cell‐fate decisions. Such coordinated regulation of differentiation processes implies that MIR8063 may participate in the cross‑talk between transcriptional regulators to influence the lineage commitments of mesenchymal, muscle, and reproductive cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its putative roles in stress and differentiation, MIR8063 may influence metabolic and hormonal networks. Investigations into Luman/CREB3 function have revealed its capacity to modulate glucocorticoid receptor signaling, mitochondrial respiration and reactive oxygen species (ROS) balance, and lipid metabolism. Collectively, these studies highlight a potential contribution of MIR8063 in maintaining energy homeostasis and adapting to metabolic stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, findings from studies in the nervous and immune systems extend the potential influence of MIR8063 to the regulation of protein translation and antigen presentation. For example, research into neuronal CPEB3‐mediated translational control—integral to long‑term synaptic plasticity—and into Luman‐regulated gene expression in dendritic cells suggests that MIR8063 might also affect post‑transcriptional and transcriptional networks that underpin memory formation and immunomodulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Timothy E Audas, Yu Li, Genqing Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel protein, Luman/CREB3 recruitment factor, inhibits Luman activation of the unfolded protein response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01439-07"}], "href": "https://doi.org/10.1128/MCB.01439-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18391022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18391022"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yanzhou Yang, Pengfei Lin, Fenglei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Luman recruiting factor regulates endoplasmic reticulum stress in mouse ovarian granulosa cell apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theriogenology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.theriogenology.2012.11.017"}], "href": "https://doi.org/10.1016/j.theriogenology.2012.11.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23270862"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23270862"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Soshi Kanemoto, Yasuhiro Kobayashi, Teruhito Yamashita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.176057"}], "href": "https://doi.org/10.1242/jcs.176057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26503158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26503158"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiangli Lan, Yaping Jin, Yanzhou Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and localization of Luman RNA and protein during mouse implantation and decidualization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Theriogenology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.theriogenology.2013.02.024"}], "href": "https://doi.org/10.1016/j.theriogenology.2013.02.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23683694"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23683694"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hyoung-Tae An, Jeonghan Kim, Seungmin Yoo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Small leucine zipper protein (sLZIP) negatively regulates skeletal muscle differentiation via interaction with α-actinin-4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.515395"}], "href": "https://doi.org/10.1074/jbc.M113.515395"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24375477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24375477"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "J Kim, J Ko "}, {"type": "b", "children": [{"type": "t", "text": "A novel PPARγ2 modulator sLZIP controls the balance between adipogenesis and osteogenesis during mesenchymal stem cell differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2014.80"}], "href": "https://doi.org/10.1038/cdd.2014.80"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24948012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24948012"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xiao Li, Pengfei Lin, Fenglei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Luman recruiting factor is involved in stromal cell proliferation during decidualization in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Tissue Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00441-016-2392-z"}], "href": "https://doi.org/10.1007/s00441-016-2392-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27053244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27053244"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Seukun Kim, Sungyeon Park, Minsoo Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of small leucine zipper protein in osteoclastogenesis and its involvement in bone remodeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2020.118827"}], "href": "https://doi.org/10.1016/j.bbamcr.2020.118827"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32822727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32822727"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jenna Penney, Ari Mendell, Minghua Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LUMAN/CREB3 is a key regulator of glucocorticoid-mediated stress responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2016.10.022"}], "href": "https://doi.org/10.1016/j.mce.2016.10.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27789393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27789393"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kentaro Oh-Hashi, Ayano Soga, Yoshihisa Naruse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elucidating post-translational regulation of mouse CREB3 in Neuro2a cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-018-3333-9"}], "href": "https://doi.org/10.1007/s11010-018-3333-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29455434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29455434"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Brandon S Smith, Kalsha H Diaguarachchige De Silva, Ashkan Hashemi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcription factor CREB3 is a potent regulator of high-fat diet-induced obesity and energy metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Obes (Lond) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41366-022-01128-w"}], "href": "https://doi.org/10.1038/s41366-022-01128-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35637262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35637262"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Brandon S Smith, Tristen Hewitt, Marica Bakovic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ER stress-associated transcription factor CREB3 is essential for normal Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": ", ATP, and ROS homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mitochondrion (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mito.2023.01.001"}], "href": "https://doi.org/10.1016/j.mito.2023.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36627030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36627030"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Briana Locke, Elena Campbell, Ray Lu "}, {"type": "b", "children": [{"type": "t", "text": "CREB3 mediates the transcriptional regulation of PGC-1α, a master regulator of energy homeostasis and mitochondrial biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.14897"}], "href": "https://doi.org/10.1002/1873-3468.14897"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38697949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38697949"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Anna Sanecka, Marleen Ansems, Maaike A van Hout-Kuijer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of genes regulated by the transcription factor LUMAN identifies ApoA4 as a target gene in dendritic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2011.12.003"}], "href": "https://doi.org/10.1016/j.molimm.2011.12.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22209087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22209087"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Lenzie Ford, Emi Ling, Eric R Kandel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CPEB3 inhibits translation of mRNA targets by localizing them to P bodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1815275116"}], "href": "https://doi.org/10.1073/pnas.1815275116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31416913"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31416913"}]}]}]}