Sandbox Reserved 1647: Difference between revisions

Line 21:

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.

Thanks to some post-translational modifications of the protein’s residues, the transcription factor TBX21 can bind with DNA between the residues <scene name='86/868180/Lys135/1'>LYS 135</scene> and <scene name='86/868180/Asn_326/1'>ASN 326</scene> 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 [https://proteopedia.org/wiki/index.php/2o93 NFAT], the one of <scene name='86/868180/Tyr304/1'>Y 304</scene> allows TBX21 to interact with [https://proteopedia.org/wiki/index.php/1co1 RUNX1], the one of <scene name='86/868180/Ser508/1'>S 508</scene> allows the interaction with [https://proteopedia.org/wiki/index.php/2i9t NF-кB p65] and finally 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 between the residues <scene name='86/868180/Lys135/1'>LYS 135</scene> and <scene name='86/868180/Asn_326/1'>ASN 326</scene> 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 <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, 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 [https://proteopedia.org/wiki/index.php/2o93 NFAT], the one of <scene name='86/868180/Tyr304/1'>Y 304</scene> allows TBX21 to interact with [https://proteopedia.org/wiki/index.php/1co1 RUNX1], the one of <scene name='86/868180/Ser508/1'>S 508</scene> allows the interaction with [https://proteopedia.org/wiki/index.php/2i9t NF-кB p65] and finally the one of Y525 allows the interaction with GATA-3.

== Biological roles of TBX21 ==

=== Regulation of Th cells differentiation by TBX21 ===

The transcription factor T-bet directs Th1 cell differentiation. The molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood but several hypotheses have already been made of the mechanism of action of T-bet.

The transcription factor T-bet directs Th1 cell differentiation. The molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood but several hypotheses have already been made of the mechanism of action of T-bet. <ref name="NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression">DOI 10.4049/jimmunol.1203403</ref>

We know that T-bet initiates Th1 lineage development from naive Thp cells by activating Th1 genetics and repressing the opposing Th2 programs. Th1 cells stimulate cellular immune response while Th2 stimulates humoral immune response and induces antibody production.

Line 42:

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 [https://en.wikipedia.org/wiki/Immunoglobulin_E 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 <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. 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 [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 (K313) of T-bet and Cysteine 424 of USP10. Deubiquitination inhibits its degradation by the proteosome and enhance the secretion of IFN- γ.

Sandbox Reserved 1647: Difference between revisions

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@@ Line 21: / Line 21: @@
 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.
-Thanks to some post-translational modifications of the protein’s residues, the transcription factor TBX21 can bind with DNA between the residues <scene name='86/868180/Lys135/1'>LYS 135</scene> and <scene name='86/868180/Asn_326/1'>ASN 326</scene> 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 [https://proteopedia.org/wiki/index.php/2o93 NFAT], the one of <scene name='86/868180/Tyr304/1'>Y 304</scene> allows TBX21 to interact with [https://proteopedia.org/wiki/index.php/1co1 RUNX1], the one of <scene name='86/868180/Ser508/1'>S 508</scene> allows the interaction with [https://proteopedia.org/wiki/index.php/2i9t NF-кB p65] and finally 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 between the residues <scene name='86/868180/Lys135/1'>LYS 135</scene> and <scene name='86/868180/Asn_326/1'>ASN 326</scene> 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 <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, 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 [https://proteopedia.org/wiki/index.php/2o93 NFAT], the one of <scene name='86/868180/Tyr304/1'>Y 304</scene> allows TBX21 to interact with [https://proteopedia.org/wiki/index.php/1co1 RUNX1], the one of <scene name='86/868180/Ser508/1'>S 508</scene> allows the interaction with [https://proteopedia.org/wiki/index.php/2i9t NF-кB p65] and finally the one of Y525 allows the interaction with GATA-3.
 == Biological roles of TBX21 ==
 === Regulation of Th cells differentiation by TBX21 ===
-The transcription factor T-bet directs Th1 cell differentiation. The molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood but several hypotheses have already been made of the mechanism of action of T-bet.
+The transcription factor T-bet directs Th1 cell differentiation. The molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood but several hypotheses have already been made of the mechanism of action of T-bet. <ref name="NFATc2 and T-bet contribute to T-helper-cell-subset-specific regulation of IL-21 expression">DOI 10.4049/jimmunol.1203403</ref>
 We know that T-bet initiates Th1 lineage development from naive Thp cells by activating Th1 genetics and repressing the opposing Th2 programs. Th1 cells stimulate cellular immune response while Th2 stimulates humoral immune response and induces antibody production.
@@ Line 42: / Line 42: @@
 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 [https://en.wikipedia.org/wiki/Immunoglobulin_E 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 <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. 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 [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 (K313) of T-bet and Cysteine 424 of USP10. Deubiquitination inhibits its degradation by the proteosome and enhance the secretion of IFN- γ.