Sandbox Reserved 1647: Difference between revisions
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=== Secondary structure and interactions === | === Secondary structure and interactions === | ||
The secondary structure of the protein allows it to bind | The secondary structure of the protein allows it to bind to DNA : the T-box domain consists of multiple <scene name='86/868180/Helix_and_strand/1'>β-strands and α-helix</scene> repeats and is involved in both dimerization and DNA binding. | ||
Thanks to some [https://en.wikipedia.org/wiki/Post-translational_modification post-translational modifications] of the protein’s residues, the transcription factor TBX21 can bind | Thanks to some [https://en.wikipedia.org/wiki/Post-translational_modification post-translational modifications] of the protein’s residues, the transcription factor TBX21 can bind to DNA between the residues <scene name='86/868180/Lys135/2'>LYS 135</scene> and <scene name='86/868180/Asn_326/4'>ASN 326</scene> and some proteins. Firstly, ubiquitination of K 313 residue allows TBX21 to bind to the DNA sequence. Lys-313 was recently found to be a key site required for the interaction of T-bet with the [https://proteopedia.org/wiki/index.php/6f1e IFN-γ] gene promoter and the phosphorylation at Thr-302 <ref name="Lysine 313 of T-box is crucial for modulation of protein stability, DNA binding, and threonine phosphorylation of T-bet">DOI 10.1073/pnas.0409512102</ref>. Secondly, phosphorylation of some residues allows TBX21 to interact with several proteins. For example, phosphorylation of T 302 allows TBX21 to interact with [https://proteopedia.org/wiki/index.php/2o93 NFAT], the one of Y 304 with [https://proteopedia.org/wiki/index.php/1co1 RUNX1], that of S 508 with [https://proteopedia.org/wiki/index.php/2i9t NF-кB p65] and finally the one of Y525 allows the interaction with <scene name='86/868180/Dna_binding_by_gata_transcript/2'>GATA-3</scene> <ref name="The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes">DOI 10.1073/pnas.0909357106</ref>. | ||
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Th1, Th2 and Th17 cells are the main cells involved in the pathophysiology of asthma <ref name="Effect of ginger extract on expression of GATA3, T-bet and ROR-γt in peripheral blood mononuclear cells of patients with Allergic Asthma">DOI 10.1016/j.aller.2018.12.003</ref>. In asthmatic airways, Th2 cells are activated and release several cytokines <ref name="The role of protein modifications of T-bet in cytokine production and differentiation of T helper cells">DOI 10.1155/2014/589672</ref> that regulate IgE production and inflammatory cell recruitment, such as eosinophils. Th2 cells and GATA-3 play an important role in allergic inflammation and asthma, and induce IgE production, which can be the cause of severe forms of asthma. The asthmatic patients present high levels of total IgE. On the contrary, the T-bet gene expression and Th1 pattern, along with the IFN- γ production, are usually associated with non-allergic asthmatics and healthy subjects <ref name="Asthma: T-bet--a master controller?">DOI 10.1016/s0960-9822(02)00830-8</ref>. Also, some research has shown that airway reactivity is moderated by corticosteroid use in asthma patients and that with this use, the TBX21 variant increases Th1 and decreases Th2 cytokine expression. Thus, TBX21 may be decisive in the therapy of asthma with inhaled corticosteroids <ref name="TBX21: A functional variant predicts improvement in asthma with the use of inhaled corticosteroids">DOI 10.1073/pnas.0408532102</ref>. | Th1, Th2 and Th17 cells are the main cells involved in the pathophysiology of asthma <ref name="Effect of ginger extract on expression of GATA3, T-bet and ROR-γt in peripheral blood mononuclear cells of patients with Allergic Asthma">DOI 10.1016/j.aller.2018.12.003</ref>. In asthmatic airways, Th2 cells are activated and release several cytokines <ref name="The role of protein modifications of T-bet in cytokine production and differentiation of T helper cells">DOI 10.1155/2014/589672</ref> that regulate IgE production and inflammatory cell recruitment, such as eosinophils. Th2 cells and GATA-3 play an important role in allergic inflammation and asthma, and induce IgE production, which can be the cause of severe forms of asthma. The asthmatic patients present high levels of total IgE. On the contrary, the T-bet gene expression and Th1 pattern, along with the IFN- γ production, are usually associated with non-allergic asthmatics and healthy subjects <ref name="Asthma: T-bet--a master controller?">DOI 10.1016/s0960-9822(02)00830-8</ref>. Also, some research has shown that airway reactivity is moderated by corticosteroid use in asthma patients and that with this use, the TBX21 variant increases Th1 and decreases Th2 cytokine expression. Thus, TBX21 may be decisive in the therapy of asthma with inhaled corticosteroids <ref name="TBX21: A functional variant predicts improvement in asthma with the use of inhaled corticosteroids">DOI 10.1073/pnas.0408532102</ref>. | ||
In T-bet structure, ubiquitination takes place at LYS 313. It has an impact on the stability of the protein and leads to the degradation of the protein by the proteosome. Some research | In T-bet structure, ubiquitination takes place at LYS 313. It has an impact on the stability of the protein and leads to the degradation of the protein by the proteosome. Some research has highlighted the role of deubiquitinases involved in T-bet stability and function. As a deubiquitinase, USP10 belongs to the ubiquitin-specificprotease family of cysteine proteases. Cysteine 424 site on [https://en.wikipedia.org/wiki/USP10 USP10] is crucial for its hydrolase activity. Results have shown that USP10 could interact with T-bet and stabilize it via interaction between Lysine 313 of T-bet and Cysteine 424 of USP10. Deubiquitination inhibits its degradation by the proteosome and enhance the secretion of IFN- γ. | ||
Researchers believe that the USP10-dependent T-bet deubiquitination and stabilization can regulate antigen induced immune disorder especially in Th1 specific inflammation. Thus, appropriate decreasing USP10 level may contribute to the T-bet degradation and inflammation attenuation <ref name="Deubiquitination and stabilization of T-bet by USP10">DOI 10.1016/j.bbrc.2014.05.037</ref>. | Researchers believe that the USP10-dependent T-bet deubiquitination and stabilization can regulate antigen induced immune disorder especially in Th1 specific inflammation. Thus, appropriate decreasing USP10 level may contribute to the T-bet degradation and inflammation attenuation <ref name="Deubiquitination and stabilization of T-bet by USP10">DOI 10.1016/j.bbrc.2014.05.037</ref>. | ||
Over the past few years, it has been shown by researchers that the polymorphism of TBX21 could act on nasal polyps and aspirin intolerance too. Patients | Over the past few years, it has been shown by researchers that the polymorphism of TBX21 could act on nasal polyps and aspirin intolerance too. Patients with both aspirin-intolerance and asthma suffer from bronchoconstriction when using aspririn. This bronchoconstriction is due to the production of cysteinyl leukotrienes, a family of inflammatory mediators, triggered by aspirin intake <ref>PMID: 512268</ref>. | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
