Sandbox Reserved 1647: Difference between revisions

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The secondary structure of the protein allows it to bind with the DNA : The T-box domain consists of several repeats of <scene name='86/868180/Helix_and_strand/1'>β-strands and α-helix</scene> and is involved in both dimerization and DNA binding. The crystal structure of the α-helices of the T-box domain bound to DNA strongly suggests that the amino group of <scene name='86/868180/Lys314/1'>K 313</scene> is associated with the phosphate of a DNA base via hydrogen-bond interaction.
The secondary structure of the protein allows it to bind with the DNA : The T-box domain consists of several repeats of <scene name='86/868180/Helix_and_strand/1'>β-strands and α-helix</scene> and is involved in both dimerization and DNA binding. The crystal structure of the α-helices of the T-box domain bound to DNA strongly suggests that the amino group of <scene name='86/868180/Lys314/1'>K 313</scene> is associated with the phosphate of a DNA base via hydrogen-bond interaction.
Thanks to some post-translational modifications of the protein’s residues, the transcription factor TBX21 can bind with DNA and some proteins. Firstly, the ubiquitination of the residue <scene name='86/868180/Lys314/1'>K 313</scene> allows TBX21 to bind with the DNA sequence. Lys-313 was lately found as a key site required for T-bet to interact with the IFN-γ gene promoter and to assure phosphorylation at Thr-302. Secondly, the phosphorylation of some residues allows TBX21 to interact with several proteins : the phosphorylation of <scene name='86/868180/Thr302/1'>T 302</scene> allows TBX21 to interact with NFAT, the one of <scene name='86/868180/Tyr304/1'>Y 304</scene> allows TBX21 to interact with RUNX1, the one of <scene name='86/868180/Ser508/1'>S 508</scene> allows the interaction with NF-кB p65 and finaly the one of Y525 allows the interaction with GATA-3.
Thanks to some post-translational modifications of the protein’s residues, the transcription factor TBX21 can bind with DNA and some proteins. Firstly, the ubiquitination of the residue <scene name='86/868180/Lys314/1'>K 313</scene> allows TBX21 to bind with the DNA sequence. Lys-313 was lately found as a key site required for T-bet to interact with the IFN-γ gene promoter and to assure phosphorylation at Thr-302. Secondly, the phosphorylation of some residues allows TBX21 to interact with several proteins : the phosphorylation of <scene name='86/868180/Thr302/1'>T 302</scene> allows TBX21 to interact with NFAT[[https://proteopedia.org/wiki/index.php/2o93]], the one of <scene name='86/868180/Tyr304/1'>Y 304</scene> allows TBX21 to interact with RUNX1[[https://proteopedia.org/wiki/index.php/1co1]], the one of <scene name='86/868180/Ser508/1'>S 508</scene> allows the interaction with NF-кB p65[[https://proteopedia.org/wiki/index.php/2i9t]] and finaly the one of Y525 allows the interaction with GATA-3.




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=== TBX21 as an antiasthmatic regulator ===
=== TBX21 as an antiasthmatic regulator ===
Asthma remains one of the commonest chronic inflammatory diseases and has a major impact on the life of sufferers. It is associated with allergy mediated by IgE antibodies.T-bet was found associated with many immune-mediated diseases such as asthma.
Asthma remains one of the commonest chronic inflammatory diseases and has a major impact on the life of sufferers. It is associated with allergy mediated by IgE antibodies[[https://proteopedia.org/wiki/index.php/2r56]].T-bet was found associated with many immune-mediated diseases such as asthma.


In asthmatic airways, Th2 cells are activated and release several cytokines 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. The asthmatic patients present high levels of total IgE[[https://proteopedia.org/wiki/index.php/2r56]]. 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.
In asthmatic airways, Th2 cells are activated and release several cytokines 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. 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.


In T-bet structure, ubiquitination takes place at <scene name='86/868180/Lys313/1'>LYS 313</scene>. It has an impact on the stability of the protein and leads to the degradation of the protein by the proteosome. Some research found 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 USP10[[https://proteopedia.org/wiki/index.php/2lbc]] is crucial for its hydrolase activity. Results have shown that USP10 could interact with T-bet and stabilize it via interaction between Lysine 313 (K313) of T-bet and Cysteine 424 of USP10. Deubiquitination inhibits its degradation by the proteosome and enhance the secretion of IFN- γ.
In T-bet structure, ubiquitination takes place at <scene name='86/868180/Lys313/1'>LYS 313</scene>. It has an impact on the stability of the protein and leads to the degradation of the protein by the proteosome. Some research found 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 USP10[[https://proteopedia.org/wiki/index.php/2lbc]] is crucial for its hydrolase activity. Results have shown that USP10 could interact with T-bet and stabilize it via interaction between Lysine 313 (K313) of T-bet and Cysteine 424 of USP10. Deubiquitination inhibits its degradation by the proteosome and enhance the secretion of IFN- γ.