Tripartite motif-containing 33 (Trim33) determines the pathogenic function of Th17 cells
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ABSTRACT:
PROVIDER: PRJNA454473 | ENA |
REPOSITORIES: ENA
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Project description:We report that Tripartite motif-containing 33 (Trim33), a protein that was previously associated with TGF-beta signaling, determines the pathogenic function of Th17 cells. Trim33 deficiency in T cells resulted in resistance to an autoimmune disease model. Lack of Trim33 did not impact TGF-beta signaling in mediating Foxp3 gene expression but greatly reduced TGF-beta induction of IL-17 production during Th17 cell differentiation. Importantly, we found TGF-beta not only increased IL-17 but also suppressed IL-10 expression; absence of Trim33 or Smad2 but not Smad4 in T cells enhanced IL-10 expression. In a Smad2-dependent manner, Trim33 was recruited to Il17 and Il10 gene loci and was crucial in appropriate histone modification accompanying Th17 differentiation. Our study thus demonstrates that Trim33, a non-canonical branch of TGF-beta signaling, programs the pro-inflammatory function of Th17 differentiation by promoting IL-17 and suppressing IL-10 expression. As a critical switch of pathogenic versus regulatory phenotype of T cells, Trim33 may be targeted in treating human autoimmune diseases.
2018-05-02 | GSE113925 | GEO
Project description:Using a proteomics approach, we identified the Tripartite Motif Containing 33 (TRIM33) as a novel transcriptional coactivator of AR. We demonstrate TRIM33 facilitates the AR chromatin binding to directly regulate a transcription program that promotes PCa progression by protecting AR from Skp2-mediated ubiquitination and proteasomal degradation. We also show TRIM33 is essential for PCa tumor growth by avoiding cell cycle arrest and apoptosis, and TRIM33 knockdown sensitizes PCa cells to AR antagonists. In clinical analyses, we find TRIM33 is upregulated in multiple PCa patient cohorts. Finally, we uncover an AR-TRIM33 coactivated gene signature that is highly expressed in PCa tumors and predicts disease recurrence. Overall, our results reveal TRIM33 is an oncogenic AR coactivator in PCa and a potential therapeutic target for PCa treatment.
2022-05-05 | GSE174109 | GEO
Project description:Using a proteomics approach, we identified the Tripartite Motif Containing 33 (TRIM33) as a novel transcriptional coactivator of AR. We demonstrate TRIM33 facilitates the AR chromatin binding to directly regulate a transcription program that promotes PCa progression by protecting AR from Skp2-mediated ubiquitination and proteasomal degradation. We also show TRIM33 is essential for PCa tumor growth by avoiding cell cycle arrest and apoptosis, and TRIM33 knockdown sensitizes PCa cells to AR antagonists. In clinical analyses, we find TRIM33 is upregulated in multiple PCa patient cohorts. Finally, we uncover an AR-TRIM33 coactivated gene signature that is highly expressed in PCa tumors and predicts disease recurrence. Overall, our results reveal TRIM33 is an oncogenic AR coactivator in PCa and a potential therapeutic target for PCa treatment.
2022-05-05 | GSE174589 | GEO
Project description:We report the genome-wide binding of Trim33 in Th17 cells. We found that more than 90% of Trim33 binding regions was located in non-conding sequence, and therefore reflect the role of Trim33 as a trancriptional co-factor. Trim33 was found to accumulate on cis-regulatory regions of genes that regulate the function of Th17 cells such as Il17a, Ccr6 and Il10. This study provides a basis for the comprehensive understanding of Trim33-mediated regulation of Th17 cells.
2018-05-08 | GSE114119 | GEO
Project description:Rattus norvegicus Trim33, tripartite motif-containing 33 [Source:RGD Symbol;Acc:1307339], is differentially expressed in 23 experiment(s);
| ENSRNOG00000018946 | ExpressionAtlas
Project description:Rattus norvegicus Trim33, tripartite motif-containing 33 [Source:RGD Symbol;Acc:1307339], is expressed in 7 baseline experiment(s);
| ENSRNOG00000018946 | ExpressionAtlas
Project description:Monodelphis domestica TRIM33, tripartite motif containing 33 [Source:NCBI gene;Acc:100033175], is expressed in 2 baseline experiment(s);
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Project description:Danio rerio trim33, tripartite motif containing 33 [Source:NCBI gene;Acc:324053], is differentially expressed in 1 experiment(s);
| ENSDARG00000016181 | ExpressionAtlas
Project description:Danio rerio trim33, tripartite motif containing 33 [Source:NCBI gene;Acc:324053], is expressed in 1 baseline experiment(s);
| ENSDARG00000016181 | ExpressionAtlas
Project description:Sus scrofa TRIM33, tripartite motif containing 33 [Source:VGNC Symbol;Acc:VGNC:98881], is differentially expressed in 2 experiment(s);
| ENSSSCG00000006757 | ExpressionAtlas