{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTespa1 (formerly queried here as FAM200B) functions as a key adaptor protein in T cell receptor (TCR) signaling during thymocyte development. It is essential for positive selection and lineage commitment of double‐positive thymocytes by associating with core TCR signaling molecules such as PLC‑γ1, Grb2, and LAT. Through its ability to recruit and interact with the inositol 1,4,5‑trisphosphate receptor type 1 (IP3R1), Tespa1 optimizes Ca2+ flux and downstream activation of the Erk–AP-1 and Ca2+–NFAT signaling pathways, ensuring proper thymocyte differentiation and maturation."}, {"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 to its role in propagating TCR signals, Tespa1 is subject to Ca2+-dependent posttranslational modification. TCR engagement and subsequent store-operated Ca2+ entry trigger the phosphorylation of Tespa1, a modification that, while not disrupting its binding to IP3R proteins, likely modulates its activity within the TCR signalosome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond T cells, Tespa1 plays critical regulatory roles in other immune cell types. In mast cells, it acts as a negative regulator by fine-tuning the balance between LAT1 and LAT2 signalosome assembly, thereby controlling degranulation and cytokine production in response to IgE cross-linking. Tespa1 also participates in T cell-dependent B cell activation by modulating CD40-associated signaling events, which affects PLC‑γ2 phosphorylation, MAPK activation, and calcium influx, ultimately shaping antibody production and germinal center formation. These functions underscore its involvement in allergic responses, asthma pathogenesis, and even autoimmune arthritis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, Tespa1 is instrumental in the maintenance of hematopoietic stem cells (HSCs) as well as leukemia stem cells (LSCs). Under stress conditions, Tespa1 expression in HSCs is upregulated, where it interacts with components such as CSN6 of the COP9 signalosome. This interaction helps to stabilize c-Myc by preventing its ubiquitination-mediated degradation, thereby sustaining self-renewal capacity. In murine models of acute myeloid leukemia, Tespa1 deficiency compromises leukemogenesis by disrupting this regulatory mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Di Wang, Mingzhu Zheng, Lei Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.2301"}], "href": "https://doi.org/10.1038/ni.2301"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22561606"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22561606"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jingjing Liang, Jun Lyu, Meng Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tespa1 regulates T cell receptor-induced calcium signals by recruiting inositol 1,4,5-trisphosphate receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms15732"}], "href": "https://doi.org/10.1038/ncomms15732"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28598420"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28598420"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jun Lyu, Pengfei Wang, Ting Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thymic-specific regulation of TCR signaling by Tespa1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Immunol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41423-019-0259-4"}], "href": "https://doi.org/10.1038/s41423-019-0259-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31316154"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31316154"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Takahiro Fujimoto, Hiroshi Matsuzaki, Masatoshi Tanaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tespa1 protein is phosphorylated in response to store-operated calcium entry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2013.02.128"}], "href": "https://doi.org/10.1016/j.bbrc.2013.02.128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23541577"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23541577"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Di Wang, Mingzhu Zheng, Yuanjun Qiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tespa1 negatively regulates FcεRI-mediated signaling and the mast cell-mediated allergic response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20140470"}], "href": "https://doi.org/10.1084/jem.20140470"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25422497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25422497"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yunliang Yao, Wei Huang, Xiaoyu Li, et al. "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Tespa1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Deficiency Dampens Thymus-Dependent B-Cell Activation and Attenuates Collagen-Induced Arthritis in Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2018.00965"}], "href": "https://doi.org/10.3389/fimmu.2018.00965"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29867947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29867947"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ruhui Yang, Guangli Wang, Lingyun Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tespa1 plays a role in the modulation of airway hyperreactivity through the IL-4/STAT6 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-020-02621-4"}], "href": "https://doi.org/10.1186/s12967-020-02621-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33228696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33228696"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yukai Lu, Lijing Yang, Mingqiang Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tespa1 facilitates hematopoietic and leukemic stem cell maintenance by restricting c-Myc degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41375-023-01880-6"}], "href": "https://doi.org/10.1038/s41375-023-01880-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36997676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36997676"}]}]}]}