Sandbox Reserved 1647: Difference between revisions

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Here, we show that T-bet acts through enhancers to allow the recruitment of Mediator and P-TEFb in the formation of the super elongation complex (SEC). Th1 genes are occupied by RNA polymerase II in Thp cells, while T-bet-mediated recruitment of P-TEFb [[https://proteopedia.org/wiki/index.php/3mi9]] and mediator [[https://proteopedia.org/wiki/index.php/Mediator]]and activates transcriptional elongation giving place to an increased differentiation of Thp into Th1.
Here, we show that T-bet acts through enhancers to allow the recruitment of Mediator and P-TEFb in the formation of the super elongation complex (SEC). Th1 genes are occupied by RNA polymerase II in Thp cells, while T-bet-mediated recruitment of P-TEFb [[https://proteopedia.org/wiki/index.php/3mi9]] and mediator [[https://proteopedia.org/wiki/index.php/Mediator]]and activates transcriptional elongation giving place to an increased differentiation of Thp into Th1.


T-bet can also regulates Th1 cell differentiation by directly initiating gamma interferon (IFN-γ) transcription and by suppressing Th2-specific transcription factor GATA-3 [[https://proteopedia.org/wiki/index.php/3dfx]]. The T-bet induced expression of IFN-γ derives Th precursor cells to differentiate into Th1 effector cells.
T-bet can also regulates Th1 cell differentiation by directly initiating gamma interferon (IFN-γ[[https://proteopedia.org/wiki/index.php/6f1e]]) transcription and by suppressing Th2-specific transcription factor GATA-3 [[https://proteopedia.org/wiki/index.php/3dfx]]. The T-bet induced expression of IFN-γ derives Th precursor cells to differentiate into Th1 effector cells.
This stimulation of IFN-γ can takes place thanks to the action of a nuclear tyrosine kinase, c-Abl. C-Abl induces phosphorylation of T-bet at tyrosine residues <scene name='86/868180/Tyr219/1'>TYR 219</scene>, <scene name='86/868180/Tyr265/1'>TYR 265</scene>, and <scene name='86/868180/Tyr304/1'>TYR 304</scene>. C-Abl phosphorylates the tyrosine residues within the T-box domain, which is the DNA-binding domain of T-bet. This phosphorylation leads to conformational changes of the T-box domain to facilitate the DNA-binding activity of T-bet and appears to play a crucial role in the IFN-γ promoter-binding activity of T-bet.
This stimulation of IFN-γ can takes place thanks to the action of a nuclear tyrosine kinase, c-Abl. C-Abl induces phosphorylation of T-bet at tyrosine residues <scene name='86/868180/Tyr219/1'>TYR 219</scene>, <scene name='86/868180/Tyr265/1'>TYR 265</scene>, and <scene name='86/868180/Tyr304/1'>TYR 304</scene>. C-Abl phosphorylates the tyrosine residues within the T-box domain, which is the DNA-binding domain of T-bet. This phosphorylation leads to conformational changes of the T-box domain to facilitate the DNA-binding activity of T-bet and appears to play a crucial role in the IFN-γ promoter-binding activity of T-bet.


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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.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. 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[[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 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 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 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.
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