{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPIB is an ETS transcription factor that plays a pivotal role in immune cell lineage commitment and differentiation. Its expression is confined predominantly to plasmacytoid dendritic cells (pDCs) and select early hematopoietic progenitors, where it is essential for pDC development while simultaneously limiting alternative lymphoid lineages including T cells, B cells, and natural killer cells. In addition, SPIB helps regulate auto‐regulatory networks in lymphocytes—for example, by repressing key plasma cell differentiation factors—and is aberrantly expressed in certain lymphoid neoplasms such as blastic plasmacytoid dendritic cell neoplasms and Waldenstrøm macroglobulinemia, where its up‐regulation is associated with differentiation arrest."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its immunoregulatory functions, SPIB also modulates viral gene expression and lymphoma cell survival. In the setting of JC virus infection, SPIB binds directly to regulatory sequences within the viral promoter/enhancer region, thereby influencing early viral gene expression—with point mutations in its binding site significantly dampening viral activity. Moreover, in activated B cell–like diffuse large B‐cell lymphoma (ABC DLBCL), SPIB collaborates with other transcription factors (such as IRF4) to repress interferon‐β production and maintain prosurvival NF‑κB signaling, a mechanism that appears to mediate resistance to therapeutic agents like lenalidomide."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn other cellular contexts, SPIB influences both antigen sampling and tumor cell behavior. Ectopic expression of SPIB in mucosal epithelial cells has been shown to activate downstream kinases like HCK, thereby enhancing apical‐to‐basolateral transcytosis—a key event in the initiation of adaptive mucosal immunity. In parallel, SPIB can act as a tumor suppressor in colorectal cancer cells by inhibiting proliferation, migration, and invasion while promoting apoptotic cell death and chemosensitivity via activation of signaling cascades (including NF‑κB and JNK) through its target MAP4K1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Remko Schotte, Marie-Clotilde Rissoan, Nathalie Bendriss-Vermare, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transcription factor Spi-B is expressed in plasmacytoid DC precursors and inhibits T-, B-, and NK-cell development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2002-02-0438"}], "href": "https://doi.org/10.1182/blood-2002-02-0438"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12393575"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12393575"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ximei Wu, Norio Itoh, Takashi Taniguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Requirement of calcium and phosphate ions in expression of sodium-dependent vitamin C transporter 2 and osteopontin in MC3T3-E1 osteoblastic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0167-4889(03)00065-x"}], "href": "https://doi.org/10.1016/s0167-4889(03"}, {"type": "t", "text": "00065-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12788230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12788230"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Remko Schotte, Maho Nagasawa, Kees Weijer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20041231"}], "href": "https://doi.org/10.1084/jem.20041231"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15583020"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15583020"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chuan-dong Geng, Wayne V Vedeckis "}, {"type": "b", "children": [{"type": "t", "text": "c-Myb and members of the c-Ets family of transcription factors act as molecular switches to mediate opposite steroid regulation of the human glucocorticoid receptor 1A promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M508245200"}], "href": "https://doi.org/10.1074/jbc.M508245200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16263717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16263717"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wendy Dontje, Remko Schotte, Tom Cupedo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Delta-like1-induced Notch1 signaling regulates the human plasmacytoid dendritic cell versus T-cell lineage decision through control of GATA-3 and Spi-B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2005-05-2090"}], "href": "https://doi.org/10.1182/blood-2005-05-2090"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16317090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16317090"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Heike Schmidlin, Sean A Diehl, Maho Nagasawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spi-B inhibits human plasma cell differentiation by repressing BLIMP1 and XBP-1 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-01-136440"}], "href": "https://doi.org/10.1182/blood-2008-01-136440"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18552212"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18552212"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Santiago Montes-Moreno, Rocio Ramos-Medina, Azahara Martínez-López, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPIB, a novel immunohistochemical marker for human blastic plasmacytoid dendritic cell neoplasms: characterization of its expression in major hematolymphoid neoplasms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-08-447599"}], "href": "https://doi.org/10.1182/blood-2012-08-447599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23165482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23165482"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yangsheng Zhou, Xia Liu, Lian Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional repression of plasma cell differentiation is orchestrated by aberrant over-expression of the ETS factor SPIB in Waldenström macroglobulinaemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Haematol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bjh.12936"}], "href": "https://doi.org/10.1111/bjh.12936"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24801987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24801987"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Leslie J Marshall, Lisa Dunham, Eugene O Major "}, {"type": "b", "children": [{"type": "t", "text": "Transcription factor Spi-B binds unique sequences present in the tandem repeat promoter/enhancer of JC virus and supports viral activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gen Virol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1099/vir.0.023184-0"}], "href": "https://doi.org/10.1099/vir.0.023184-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20826618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20826618"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Leslie J Marshall, Lisa D Moore, Matthew M Mirsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "JC virus promoter/enhancers contain TATA box-associated Spi-B-binding sites that support early viral gene expression in primary astrocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Gen Virol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1099/vir.0.035832-0"}], "href": "https://doi.org/10.1099/vir.0.035832-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22071512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22071512"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yibin Yang, Arthur L Shaffer, N C Tolga Emre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2012.05.024"}], "href": "https://doi.org/10.1016/j.ccr.2012.05.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22698399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22698399"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Tsuneaki Asai, Sherie L Morrison "}, {"type": "b", "children": [{"type": "t", "text": "The SRC family tyrosine kinase HCK and the ETS family transcription factors SPIB and EHF regulate transcytosis across a human follicle-associated epithelium model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.437475"}], "href": "https://doi.org/10.1074/jbc.M112.437475"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23439650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23439650"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Xunping Zhao, Lin Li, Shiyun Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPIB acts as a tumor suppressor by activating the NFkB and JNK signaling pathways through MAP4K1 in colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2021.110148"}], "href": "https://doi.org/10.1016/j.cellsig.2021.110148"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34530056"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34530056"}]}]}]}