HnRNPA1 SUMOylation promotes cold hypersensitivity in chronic inflammatory pain by stabilizing TRPA1 mRNA
Ontology highlight
ABSTRACT:
ORGANISM(S): Cricetulus Griseus
SUBMITTER: 
Yong Li
PROVIDER: PXD046198 | iProX | Wed Oct 18 00:00:00 BST 2023
REPOSITORIES: iProX
Similar Datasets
Project description:We show here that the up-regulation of SUMO1-conjugated protein levels in a CFA-induced inflammatory pain model enhances TRPA1 mRNA stability, ultimately leading to increased expression levels.
2023-10-18 | PXD046199 | iProX
Project description:Transcription related proteins are among the most frequently identified targets of SUMO post-translational modification, but the gene-specific and genome-wide effects of transcription machinery sumoylation are not well-understood. To explore this, we examined whether dramatically reducing cellular sumoylation levels affects the levels of mRNAs in budding yeast. RNA-seq was performed using polyadenylate (polyA)-enriched RNAs from the sumoylation-deficient ubc9-6 strain and its wild-type parent. Indeed, the abundance of hundreds of mRNAs were upregulated or downregulated in the mutant strain, implying that sumoylation has a widespread influence on RNA polymerase II (RNAPII) transcription or mRNA stability. Interestingly, about one third of mRNAs that were significantly upregulated in the ubc9-6 strain encode proteins that are involved in small molecule metabolic processes, suggesting that sumoylation is normally involved in restricting these pathways. As part of our analysis of transcription-related sumoylation, we determined that the large subunit of TFIIF, Tfg1, is a major target of sumoylation among the general transcription factors (GTFs) of RNAPII. To determine whether sumoylation of Tfg1 specifically is involved in regulating mRNA levels, we performed RNA-seq on polyA-enriched RNAs derived from strains expressing wild-type (Tfg1-HA) or sumoylation-deficient (Tfg1-K60,61R-HA) forms of Tfg1. However, with few exceptions, impairing Tfg1 sumoylation had no effect on the mRNA transcriptome. Together, our data demonstrate that gene expression is extensively regulated by sumoylation, but this likely involves the coordinated modification of multiple proteins at multiple levels.
2021-09-21 | GSE167427 | GEO
Project description:To examine the functional significance of TRPV1 SUMOylation in vivo, we created a TRPV1K823R KI transgenic mouse line.We thus performed gene expression profiling analysis using data obtained from RNA-seq of the trigeminal ganglion of TRPV1K823R and control mouse models . Our analyses unveiled a role for TRPV1 SUMOylation in regulating gene networks related to the pain and itch pathway.
2022-06-14 | GSE203197 | GEO
Project description:Phylogenetically conserved lysines 419 and 845 of zebrafish Zbtb21 protein can be conjugated with SUMO molecules. SUMOylation does not affect the subcellular localization and protein stability of Zbtb21, as well as the interaction with Zbtb14 or Zbtb21. Nevertheless, luciferase reporter assays revealed that Zbtb21 is a dual-function transcription factor which exerts activation or repression effect on different promoters, and SUMOylation can modulate the transcriptional activity of Zbtb21 in regulating downstream target genes. Hence, Zbtb21 is identified as a novel substrate of SUMOylation, which would be important for its function.
2024-04-06 | GSE254892 | GEO
Project description:Phylogenetically conserved lysines 419 and 845 of zebrafish Zbtb21 protein can be conjugated with SUMO molecules. SUMOylation does not affect the subcellular localization and protein stability of Zbtb21, as well as the interaction with Zbtb14 or Zbtb21. Nevertheless, luciferase reporter assays revealed that Zbtb21 is a dual-function transcription factor which exerts activation or repression effect on different promoters, and SUMOylation can modulate the transcriptional activity of Zbtb21 in regulating downstream target genes. Hence, Zbtb21 is identified as a novel substrate of SUMOylation, which would be important for its function.
2024-04-06 | GSE255803 | GEO
Project description:SUMOylation is a dynamic post-translational protein modification that primarily takes place in cell nuclei, where it plays a key role in multiple DNA-related processes. In brain cells, and particularly in neurons, mostly nuclear proteins are SUMOylated, and the SUMOylation-dependent control of a subset of neuronal transcription factors is known to regulate various aspects of nerve cell differentiation, development, and function. In an unbiased screen for endogenous SUMOylation targets in the developing mouse brain, we previously identified the transcription factor Zbtb20 as a new SUMO1 conjugate. We show here that the three key SUMO paralogues SUMO1, SUMO2, and SUMO3 can all be conjugated to Zbtb20 in vitro, and we confirm the SUMOylation of Zbtb20 in vivo. Using primary hippocampal neurons as a model system, we then demonstrate that the expression of Zbtb20 is required for proper nerve cell development and neurite growth and branching. Furthermore, we show that the SUMOylation of Zbtb20 is essential for Zbtb20 function in this context, and provide evidence indicating that SUMOylation affects the Zbtb20-dependent transcriptional profile of neurons. Taken together, our data highlight the role of SUMOylation in the regulation of neuronal transcription factors that determine nerve cell development. Specifically, our data demonstrate that key functions of the transcription factor Zbtb20 in neuronal development and neurite growth are under the obligatory control of SUMOylation.
2021-01-06 | GSE143926 | GEO
Project description:Post-translational modification with SUMO is known to regulate the activity of transcription factors, but how SUMOylation of individual proteins might influence immunity is mostly unexplored. The NFAT transcription factors play an essential role in antigen receptor-mediated gene regulation. SUMOylation of NFATc1 represses IL-2 in vitro, but its role in T cell-mediated immune responses in vivo is not clear. To this end, we generated a novel Nfatc1 transgenic mouse, which prevents SUMO modification of NFATc1. Avoidance of NFATc1 SUMOylation ameliorated experimental autoimmune encephalomyelitis as well as graft-versus-host disease. An elevated IL-2 production promoted Treg expansion and suppressed autoreactive or alloreactive T cells. Mechanistically, increased IL-2 secretion counteracted IL-17 and IFN-γ expression through STAT5 and Blimp-1 induction. Then, Blimp-1 repressed IL-2 itself and the as well induced, proliferation-associated survival factor Bcl2A1. Collectively, we demonstrate that prevention of NFATc1 SUMOylation fine-tunes T-cell responses towards lasting tolerance. Thus, targeting NFATc1 SUMOylation presents a novel and promising strategy to treat T cell-mediated inflammatory diseases.
2020-07-01 | GSE148087 | GEO
Project description:Background: Adenovirus protein Gam1 triggers the proteolytic destruction of the E1 SUMO-activating enzyme. Microinjection of an empirically determined amount of Gam1 mRNA into one-cell Xenopus embryos can reduce SUMOylation activity to undetectable, but nonlethal levels, enabling an examination of the role of this post-translational modification during early vertebrate development. Results: We find that SUMOylation-deficient embryos consistently exhibit defects in neural tube and heart development. We have measured differences in gene expression between control and embryos injected with Gam1 mRNA at three developmental stages: early gastrula (immediately following the initiation of zygotic transcription), late gastrula (completion of the formation of the three primary germ layers), and early neurula (appearance of the neural plate). Although changes in gene expression are widespread and can be linked to many biological processes, three pathways, non-canonical Wnt/PCP, snail/twist, and Ets-1, are especially sensitive to the loss of SUMOylation activity and can largely account for the predominant phenotypes of Gam1 embryos. SUMOylation appears to generate different pools of a given transcription factor having different specificities with this post-translational modification involved in the regulation of more complex as opposed to housekeeping processes. Conclusions: We have identified changes in gene expression that underlie the neural tube and heart phenotypes resulting from depressed SUMOylation activity. Notably, these developmental defects correspond to the two most frequently occurring congenital birth defects in humans, strongly suggesting that perturbation of SUMOylation, either globally or of a specific protein, may frequently be the origin of these pathologies.
2018-06-23 | GSE116164 | GEO
Project description:Cortisol, the central stress hormone in humans, activates the glucocorticoid receptor (GR). Anti-inflammatory effects are the most important pharmaceutical effects mediated by the GR. Inasmuch as electrophilic cyclopentenone prostaglandin 15-deoxy-M-NM-^T12,14-prostaglandin J2 (15d-PGJ2) has potent anti-inflammatory properties and activates the SUMOylation pathway, we have investigated the effect of 15d-PGJ2 on glucocorticoid signaling and receptor SUMOylation. To this end, we studied isogenic HEK293 cells expressing either wild-type GR or SUMOylation-defective GR. Interestingly, 15d-PGJ2 triggered SUMO-2/3 modification in the primary SUMOylation sites of the GR. Gene expression profiling and pathway analyses indicate that 15d-PGJ2 inhibits GR signaling in a genome-wide fashion that is significantly dependent on the GR SUMOylation sites. Chromatin immunoprecipitation assays showed that the repressive effect of 15d-PGJ2 on GR target gene expression occurs in parallel with the inhibition of receptor binding to the target gene chromatin. Furthermore, depletion of the sole SUMO E2 conjugase UBC9 from HEK293 cells confirmed the involvement of active SUMOylation in the regulatory process. Taken together, our data indicate that GR SUMOylation modulates the glucocorticoid signaling during acute cell stress. Our data also suggest that GR SUMOylation modulates crosstalk of the glucocorticoid signaling with other transcription factors that are responsive to cell stress. Total RNA isolated from isogenic HEK293 cell lines stably expressing either wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR) treated with 100 nM of dexamethasone (dex) in the presence or absence of 5 M-BM-5M 15d-PGJ2 for 6h. All conditions are performed in triplicate
2014-06-30 | E-GEOD-54087 | biostudies-arrayexpress
Project description:Genome wide localization of SUMO1 and SUMO2/3 proteins revealed an asscociation of SUMO proetins with active chromatin. SUMO proteins are enriched at super enhancers and enhancers and SUMOylation regulates a subset of these super enhancers. Super enhancers regulated by SUMOylation were enriched for transcription factor TFAP2C and SUMOylation negatively regulates TFAP2C localization to enhancers and super enhancers. Proteomics and ChIP-PCR at MYC SE suggests that chromatin bound TFAP2C recruits histone deacetylation complexes that increases upon SAE2 knockdown. Conversely, SUMOylation promoted TFAP2C asscociation with pre-mRNA splicing machinery components. Taken together, our study revealed a critical role of SUMOylation in chromatin modification through an AP-2 family of transcription factor, TFAP2C and a potential role of TFAP2C in pre-mRNA splicing.
2024-04-13 | GSE171804 | GEO