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Beschreibung

Thymocyte selection-associated high mobility group box protein TOX (UniProt: O94900, also known as Thymus high mobility group box protein TOX) is encoded by the TOX (also known as KIAA0808) gene (Gene ID: 9760) in human. TOX is a member of an evolutionarily conserved DNA-binding protein family that plays multiple roles in the development of the adaptive immune system. It acts as a developmental checkpoint and regulates thymocyte positive selection toward T cell lineage commitment. It is required for the development of various T cell subsets, including CD4+ helper T-cells, CD8+ cytotoxic T-cells, regulatory T-cells, and CD1D-dependent natural killer T (NKT) cells. Its nuclear localization signal lies in amino acids 237-256 and the DNA-binding region (HMG box) resides in amino acids 161-329. TOX serves as a DNA-binding factor that regulates transcription by modifying local chromatin structure and modulating the formation of multi-protein complexes. It binds to GC-rich DNA sequences in the proximity of transcription start sites to alter chromatin structure and modify access of transcription factors to DNA. It also plays a major role in neural stem cell commitment and corticogenesis. During cortical development, it controls the neural stem cell pool by inhibiting the switch from proliferative to differentiating progenitors. It also promotes neurite outgrowth in newborn neurons migrating to reach the cortical plate. In T-cell lymphomas high TOX expression has been described in all the Mycosis fungoides (MF). A majority of precursor B/T lymphoblastic, follicular and diffuse large B-cell lymphomas, nodular lymphocyte-predominant Hodgkin lymphomas and angioimmunoblastic T-cell lymphomas strongly expressed the TOX protein. (Ref.: Maestre, L., et al. (2020). PLoS ONE 15(2), e0229743, Yun, S., et al. (2011). Immunol. Lett. 136(1), 29-36).