{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CYTIP, also known as cytohesin‐binding protein, CASP, or Cybr, is an adaptor molecule primarily expressed in hematopoietic and immune cells that modulates signal transduction, cellular adhesion, and migration. Its expression is induced by cytokines and is dynamically regulated during immune cell maturation. In dendritic cells, CYTIP plays a key role in deactivating the integrin LFA‐1, thereby fine‐tuning the duration of DC–T cell contacts and ultimately influencing antigen presentation and T‐cell activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Furthermore, viral infections such as HSV‐1 can trigger rapid degradation of CYTIP in DCs, resulting in increased integrin activity and impaired migratory capacity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In T lymphocytes, CYTIP modulates T cell receptor signaling by regulating cascades such as the p38 MAP kinase pathway, which affects the expression of transcription factors like T‐bet and the production of cytokines including IFN‐γ."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " While CYTIP has been implicated in enhancing lymphocyte adhesion and contributing to proper T cell activation, genetic studies indicate that its role in hematopoietic cell development may be redundant or context‐dependent."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In natural killer (NK) cells, CYTIP (CASP) participates in regulating cell motility, polarization, and cytokine secretion—particularly affecting IFN‐γ release—without altering granule‐mediated cytotoxicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, CYTIP has been observed to interact with sorting nexin 27, suggesting a possible role in intracellular trafficking events within lymphocytes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its immunological functions, epigenetic modulation of CYTIP expression has been linked to cancer progression. In clear cell renal carcinoma, for instance, loss of DNA methylation enables hypoxia‐induced CYTIP expression, which helps protect cancer cells from death cytokine signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore CYTIP’s multifaceted role in fine‐tuning immune cell adhesion, migration, and signaling, with significant implications for both immune regulation and tumor cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sandra Balkow, Stefanie Heinz, Patricia Schmidbauer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LFA-1 activity state on dendritic cells regulates contact duration with T cells and promotes T-cell priming."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-05-224428"}], "href": "https://doi.org/10.1182/blood-2009-05-224428"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20530790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20530790"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alexandros A Theodoridis, Christina Eich, Carl G Figdor, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Infection of dendritic cells with herpes simplex virus type 1 induces rapid degradation of CYTIP, thereby modulating adhesion and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-07-294363"}], "href": "https://doi.org/10.1182/blood-2010-07-294363"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21562043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21562043"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Valeska Heib, Florian Sparber, Christoph H Tripp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytip regulates dendritic-cell function in contact hypersensitivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.201041286"}], "href": "https://doi.org/10.1002/eji.201041286"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22488362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22488362"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qian Chen, Alan Coffey, Sylvain G Bourgoin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytohesin binder and regulator augments T cell receptor-induced nuclear factor of activated T Cells.AP-1 activation through regulation of the JNK pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M601629200"}], "href": "https://doi.org/10.1074/jbc.M601629200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16702224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16702224"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shu-Lin Chang, C Lee-Tian Chang, Pei-Ing Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Cybr, a cytohesin binder and regulator, in CD4(+) T-cell function and host immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2009.08.014"}], "href": "https://doi.org/10.1016/j.molimm.2009.08.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19744714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19744714"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wendy T Watford, Denise Li, Davide Agnello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytohesin binder and regulator (cybr) is not essential for T- and dendritic-cell activation and differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.02460-05"}], "href": "https://doi.org/10.1128/MCB.02460-05"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16914744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16914744"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Vincenzo Coppola, Colleen A Barrick, Sara Bobisse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The scaffold protein Cybr is required for cytokine-modulated trafficking of leukocytes in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.02473-05"}], "href": "https://doi.org/10.1128/MCB.02473-05"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16809763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16809763"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nicholas Tompkins, Brian MacKenzie, Collin Ward, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytohesin-associated scaffolding protein (CASP) is involved in migration and IFN-γ secretion in natural killer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.07.065"}], "href": "https://doi.org/10.1016/j.bbrc.2014.07.065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25058460"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25058460"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Nicholas Tompkins, Adam J MacNeil, Bill Pohajdak "}, {"type": "b", "children": [{"type": "t", "text": "Cytohesin-associated scaffolding protein (CASP) is a substrate for granzyme B and ubiquitination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.08.088"}], "href": "https://doi.org/10.1016/j.bbrc.2014.08.088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25159843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25159843"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Adam J MacNeil, Marc Mansour, Bill Pohajdak "}, {"type": "b", "children": [{"type": "t", "text": "Sorting nexin 27 interacts with the Cytohesin associated scaffolding protein (CASP) in lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2007.05.162"}], "href": "https://doi.org/10.1016/j.bbrc.2007.05.162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17577583"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17577583"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sakari Vanharanta, Weiping Shu, Fabienne Brenet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3029"}], "href": "https://doi.org/10.1038/nm.3029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23223005"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23223005"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Thomas Boehm, Susanne Hofer, Patricia Winklehner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Attenuation of cell adhesion in lymphocytes is regulated by CYTIP, a protein which mediates signal complex sequestration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdg101"}], "href": "https://doi.org/10.1093/emboj/cdg101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12606567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12606567"}]}]}]}