{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LRRC59 is a multifunctional, membrane‐anchored protein that localizes predominantly to the endoplasmic reticulum (ER) and nuclear envelope (NE), where it plays several roles in intracellular trafficking and signaling. In growth‐regulatory contexts, LRRC59 is essential for the nuclear import of specific cargos—for example, it facilitates the translocation of exogenous fibroblast growth factor 1 (FGF1) from endocytic vesicles into the nucleus by interacting with nuclear transport factors such as karyopherins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, LRRC59 mediates the nuclear entry of cytoplasmic ketohexokinase‐A under fructose stimulation, a process that triggers phosphorylation events promoting breast cancer cell invasion and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to these functions, LRRC59 plays a role in regulating oncogenic signaling and the cell cycle. It interacts with factors such as CIP2A to promote their nuclear localization, a process that contributes to aberrant mitotic progression and tumor aggressiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, LRRC59 influences innate immune responses by binding to ISG15‐associated DDX58, thereby blocking its targeting for autophagic degradation and enhancing type I interferon signaling during viral infection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Proteomic analyses have further revealed that LRRC59 is a ribosome‐binding, integral membrane protein enriched in components of the signal recognition particle (SRP) pathway and translation factors, which links it to the regulation of ER‐localized mRNA translation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Its targeting to the inner nuclear membrane appears to be governed by features of its cytosolic domain, allowing passive diffusion that bypasses the classical nuclear import machinery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Clinically, elevated levels of LRRC59 have been associated with poor prognoses in several cancers—including triple‐negative breast cancer and lung adenocarcinoma—where its overexpression correlates with enhanced cell proliferation, migration, invasion, and lymph node metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies indicate that LRRC59 functions as a central adaptor protein that coordinates nuclear transport, immune signaling, and translation processes. By ensuring the proper localization and activity of growth factors, oncogenes, and components of innate immunity, LRRC59 significantly impacts cell proliferation, survival, and oncogenic progression.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yan Zhen, Vigdis Sørensen, Camilla S Skjerpen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear import of exogenous FGF1 requires the ER-protein LRRC59 and the importins Kpnα1 and Kpnβ1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2012.01341.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2012.01341.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22321063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22321063"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jiyoung Kim, Jengmin Kang, Ye-Lim Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-19263-1"}], "href": "https://doi.org/10.1038/s41467-020-19263-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33116123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33116123"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rajash Pallai, Aishwarya Bhaskar, Natalie Barnett-Bernodat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leucine-rich repeat-containing protein 59 mediates nuclear import of cancerous inhibitor of PP2A in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3326-1"}], "href": "https://doi.org/10.1007/s13277-015-3326-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25833693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25833693"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rajash Pallai, Aishwarya Bhaskar, Natalie Barnett-Bernodat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cancerous inhibitor of protein phosphatase 2A promotes premature chromosome segregation and aneuploidy in prostate cancer cells through association with shugoshin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3284-7"}], "href": "https://doi.org/10.1007/s13277-015-3284-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25736928"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25736928"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Huifang Xian, Shuai Yang, Shouheng Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRRC59 modulates type I interferon signaling by restraining the SQSTM1/p62-mediated autophagic degradation of pattern recognition receptor DDX58/RIG-I."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2019.1615303"}], "href": "https://doi.org/10.1080/15548627.2019.1615303"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31068071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31068071"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Molly M Hannigan, Alyson M Hoffman, J Will Thompson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative Proteomics Links the LRRC59 Interactome to mRNA Translation on the ER Membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.RA120.002228"}], "href": "https://doi.org/10.1074/mcp.RA120.002228"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32788342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32788342"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Marina Blenski, Ralph H Kehlenbach "}, {"type": "b", "children": [{"type": "t", "text": "Targeting of LRRC59 to the Endoplasmic Reticulum and the Inner Nuclear Membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms20020334"}], "href": "https://doi.org/10.3390/ijms20020334"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30650545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30650545"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hiroko Toda, Sasagu Kurozumi, Yuko Kijima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-018-0510-3"}], "href": "https://doi.org/10.1038/s10038-018-0510-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30228364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30228364"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Elisa Maurizio, Jacek R Wiśniewski, Yari Ciani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Translating Proteomic Into Functional Data: An High Mobility Group A1 (HMGA1) Proteomic Signature Has Prognostic Value in Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M115.050401"}], "href": "https://doi.org/10.1074/mcp.M115.050401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26527623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26527623"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Dong Li, Ying Xing, Tiannv Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of LRRC59 Is Associated with Poor Prognosis and Promotes Cell Proliferation and Invasion in Lung Adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Onco Targets Ther (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/OTT.S245336"}], "href": "https://doi.org/10.2147/OTT.S245336"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32753886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32753886"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xiaoxi Liu, Jingjing Liu, Joshua D Lester, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ABCD2 identifies a subclass of peroxisomes in mouse adipose tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.11.046"}], "href": "https://doi.org/10.1016/j.bbrc.2014.11.046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25446110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25446110"}]}]}]}