Effect of Trim21 knockdown on MAPK and ERBB signaling pathways
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA860116 | ENA |
REPOSITORIES: ENA
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Project description:To investigate Trim21 knockdown on the gene expression of downstream effectors of MAPK and ERBB pathways, we established HPAC cell lines with Trim21 knockdown.
2023-08-08 | GSE208568 | GEO
Project description:Bortezomib (bort) is an effective therapeutic agent for multiple myeloma (MM) patients; however, the majority of patients develop drug resistance. Autophagy, a highly conserved process that recycles cytosol or entire organelles via lysosomal activity, is essential for the survival, homeostasis and drug resistance in MM. Growing evidence has highlighted that E3 ligase tripartite motif-containing protein 21 (TRIM21) not only interacts with multiple autophagy regulators but also participates in drug resistance in various cancers. However, to date, the direct substrates and additional roles of TRIM21 in MM remain unexplored. In this study, we demonstrated that low TRIM21 expression is a factor for relapse in MM. TRIM21 knockdown (KD) made MM cells more resistant to bort, while TRIM21 overexpression (OE) resulted in increased MM sensitivity to bort. Proteomic and phospho-proteomic studies of TRIM21 KD MM cells showed that bort resistance was associated with increased oxidative stress and elevated pro-survival autophagy. Our results provided that TRIM21 KD MM cell lines induced pro-survival autophagy after bort treatment, and suppressing autophagy by 3-methyladenine treatment or by the short hairpin RNA of ATG5 restored bort sensitivity. Indeed, autophagy-related gene 5 (ATG5) expression was increased and decreased by TRIM21 KD and OE, respectively. TRIM21 affected autophagy by ubiquitinating ATG5 through K48 for proteasomal degradation. Importantly, we confirmed that TRIM21 could potentiate the anti-myeloma effect of bort through in vitro and in vivo experiments. Overall, our findings define the key role of TRIM21 in MM bort resistance and provide a foundation for a novel targeted therapeutic approaches.
2023-10-24 | PXD042004 | Pride
Project description:Macrophage polarization followed by acute myocardial infarction (MI) is essential for the regulation of inflammation and scar formation. Tripartite motif-containing protein 21 (TRIM21), a member of E3 ubiquitin ligases, is a crucial mediator in the process of inflammation and heart failure. However, the potential roles of TRIM21 in modulating post-MI inflammation and macrophage polarization remain elusive. We detected that the levels of TRIM21 were significantly reduced in macrophages of WT mice after MI. In contrast, MI was ameliorated in TRIM21 knockout (TRIM21-/-) mice with improved cardiac remodeling, characterized by a marked decrease in mortality, increased wall thickness, and improved cardiac function in comparison with wild-type (WT) MI mice. Importantly, TRIM21 deficiency decreased the post-MI apoptosis and DNA damage in the hearts of mice, and the accumulation of M1 phenotype macrophages in infarcted hearts significantly decreased in TRIM21-/- mice compared with WT controls. Mechanistically, depletion of TRIM21 orchestrated the process of M1 macrophage polarization via a PI3K/Akt signaling pathway. Overall, these data reveal that TRIM21 drives the inflammatory response and cardiac remodeling after MI via stimulating M1 macrophage polarization through a PI3K/Akt signaling pathway.
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Project description:In order to better understand signaling events following receptor dimerization involving HER2, we have generated an experimental system in which ErbB dimerization can be controlled. We used gene expression microarrays to identify genes and pathways that are differentially activated by HER2 homodimers and HER2 containing heterodimers.
2011-05-13 | GSE22288 | GEO
Project description:In order to better understand signaling events following receptor dimerization involving HER2, we have generated an experimental system in which ErbB dimerization can be controlled. We used gene expression microarrays to identify genes and pathways that are differentially activated by HER2 homodimers and HER2 containing heterodimers. MCF10A-HER2-FKBP-HA cells were treated with AP1510, TGFalpha or heregulin for 48 hrs prior to RNA harvest for array analysis.
2011-05-13 | E-GEOD-22288 | biostudies-arrayexpress
Project description:The present study comprehensively revealed the molecular characteristics in relation to OC and identified significantly distinct phosphorylated sites and phosphorylated proteins underlying the syndrome. The results here dissected regulatory elements (especially kinases) and pathways involved in cancer-related pathways including fructose & mannose metabolism, MAPK, ErbB, and ErbB signaling pathway. These findings may not only provide potential biomarkers and novel therapeutic targets for OC, but also bolstered our knowledge on the physiopathology of this syndrome.
2019-12-31 | PXD016183 |
Project description:This is A431 IERMv1.0 model described in the article
Input-output behavior of ErbB signaling pathways as revealed by a mass action model trained against dynamic data.
William W Chen, Birgit Schoeberl, Paul J Jasper, Mario Niepel, Ulrik B Nielsen, Douglas A Lauffenburger and Peter K Sorger. Molecular Systems Biology
2009; 5:239. PMID: 19156131
, DOI: 10.1038/msb.2008.74
Abstract:
The ErbB signaling pathways, which regulate diverse physiological responses such as cell survival, proliferation and motility, have been subjected to extensive molecular analysis. Nonetheless, it remains poorly understood how different ligands induce different responses and how this is affected by oncogenic mutations. To quantify signal flow through ErbB-activated pathways we have constructed, trained and analyzed a mass action model of immediate-early signaling involving ErbB1-4 receptors (EGFR, HER2/Neu2, ErbB3 and ErbB4), and the MAPK and PI3K/Akt cascades. We find that parameter sensitivity is strongly dependent on the feature (e.g. ERK or Akt activation) or condition (e.g. EGF or heregulin stimulation) under examination and that this context dependence is informative with respect to mechanisms of signal propagation. Modeling predicts log-linear amplification so that significant ERK and Akt activation is observed at ligand concentrations far below the K(d) for receptor binding. However, MAPK and Akt modules isolated from the ErbB model continue to exhibit switch-like responses. Thus, key system-wide features of ErbB signaling arise from nonlinear interaction among signaling elements, the properties of which appear quite different in context and in isolation.
The sbml model is available as supplemental material to the article and at http://www.cdpcenter.org/resources/models/chen-et-al-2008/
. It was slightly changed to make it valid SBML and to incorporate the step functions, described in the readme file and needed for inhibitor preincubation. the equilibration processes end at 1800 sec, so to reproduce the dynamics shown in the publication and supplemental material, only the time points after 1800 need to be considered. The parameter set is the hand fitted one used for Sfigure 3 in the supplemental materials. All species are in molecules, apart from HRG, EGF and Inh, which are in M.
The results shown in SFigure 3 can be calculated dividing the parameters ERK_PP
, AKT_PP
and ERB_B1_P_tot
by ERK_t
, AKT_t
and EGFR_t
, respectively. Somehow we did not find the right scaleing factor for the phosphorylated ErbB1 receptor. Therefore the model does only qualitatively reproduces the timecourses shown in the first row of Sfigure 3.
This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.
For more information see the terms of use
.
To cite BioModels Database, please use Le Nov������re N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.
2024-09-02 | BIOMD0000000255 | BioModels
Project description:We make Pa01c cells stable expressing a scramble or shRNA against TRIM21 and performed bulk scRNASeq to assess transcriptomic changes Pa01c cells
2024-11-21 | GSE207852 | GEO
Project description:Acute response to diethylnitrosamine treatment in TRIM21 wild-type and knockout mice were compared and differentially expressed genes were inendified at 48 hours
2021-04-14 | GSE164369 | GEO