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 | GSE174589 | 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: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:Myocardial fibrosis, a common pathological manifestation of cardiac remodeling (CR), often leads to heart failure (HF) and even death. The underlying molecular mechanism of the role of TRIM33 in Ang II-induced myocardial fibrosis is not fully understood. We found that TRIM33 was specifically upregulated in CFs and myocardial tissue after Ang II stimulation. Adult mice induced by Ang II were used as in vivo models, and Ang II-induced neonatal mouse primary cardiac fibroblasts (CFs) were used as in vitro models. The level of CF fibrosis in vitro was assessed by CF proliferation, migration, activation and extracellular matrix (ECM) synthesis. In addition, Masson staining, the heart weight/body weight (HW/BW) ratio and echocardiography were used to evaluate the in vivo effect of TRIM33. TRIM33 expression was specifically upregulated in CFs and myocardial tissue after Ang II stimulation. In in vitro experiments, we found that TRIM33 knockdown promoted Ang II-induced CF proliferation, while TRIM33 overexpression weakened Ang II-induced CF proliferation, migration, activation and collagen synthesis. Mechanistically, we showed that TRIM33, negatively regulated by HSPB5, mediated its antifibrotic effect by inhibiting the activation of TGF-β1 and its downstream genes, Smad3 and Smad4. Finally, TRIM33 overexpression suppressed fibrosis and promoted cardiac repair and functional recovery in Ang II-induced mice. Our results clearly establish that TRIM33 limits cardiac fibrosis by hindering CF proliferation, migration, activation and collagen synthesis. Enhancing these beneficial functions of TRIM33 by a targeting vector might be a novel therapeutic strategy for CR.
| S-EPMC9161881 | biostudies-literature
Project description:We report high throughput profiling and co-occupancy of Trim33, Ctcf and H3K27ac in differentiating embryoid bodies derived from mouse embryonic stem cells. An average of ~37 million reads were generated for each of the described samples and input sample generating 4,426, 52,446, 30,047 peaks respectively for Trim33, CTCF and H3K27ac. Motif enrichment analyses for Trim33 ChiP-Seq data returned CTCF and BORIS (CTCF analog) motifs as best matches. Of the merged peaks, 723 were shared by Trim33, CTCF as well as H3K27ac. In addition, 1299 peaks were shared by Trim33 and CTCF, 1131 were shared by Trim33 and H3K27ac and 3321 were shared by CTCF and H3K27ac.
2019-01-01 | GSE119874 | GEO
Project description:To get insight into TRIM33 functions, TRIM33 ChIP-seq was carried out in murine macrophage cell line (RAW) and in bone marrow-derived macrophages (BMDM). The results showed that, in addition to its role in hematopoietic differentiation, TRIM33 may modulate PU.1 transcriptional activity during macrophage development and/or activation.To characterize the role of TRIM33 in macrophages, we bred TRIM33fl/fl mice with Lyz-Cre mice where the Cre recombinase gene is under the regulatory sequences of the Lyz gene that is expressed only in mature myeloid cells. Bone marrow cells from LyzCre/Trim33+/+ mice and LyzCre/Trim33flox/flox mice were differentiated in macrophages and treated during 0h, 4h, 12h and 24h with LPS. Using ChIP-seq, we provide a link between TRIM33 binding and H3K4me3 spreading on inflammatory genes in macrophages. Chromatin immunoprecipitations of TRIM33 and H3K4Me3 followed by multiparallel sequencing performed in murine bone marrow-derived macrophages (BMDM).
2015-11-23 | E-GEOD-43654 | biostudies-arrayexpress
Project description:Autophagy is a cellular degradative process that has multiple important actions in cancer. Autophagy modulation is under consideration as a promising new approach to cancer therapy. However, complete autophagy dysregulation is likely to have substantial undesirable side effects. Thus, more targeted approaches to autophagy modulation may prove clinically beneficial. One potential avenue to achieving this goal is to focus on the actions of tripartite motif-containing protein family members (TRIMs). TRIMs have key roles in an array of cellular processes, and their dysregulation has been extensively linked to cancer risk and prognosis. As detailed here, emerging data shows that TRIMs can play important yet context-dependent roles in controlling autophagy and in the selective targeting of autophagic substrates. This review covers how the autophagy-related actions of TRIM proteins contribute to cancer and the possibility of targeting TRIM-directed autophagy in cancer therapy.
| S-EPMC7081753 | biostudies-literature
Project description:Tripartite motif 8 promotes hepatocellular carcinogenesis by mediating ubiquitination and degradation of hepatocyte nuclear factor 1α
| PRJNA990674 | ENA
Project description:Genomewide mapping of Trim33 binding in Th17 cells
| PRJNA464365 | ENA