Similar Datasets
Project description:To establish molecular pathways disrupted by loss of RREB1 in Purkinje cells, RNA-seq was performed on mRNA isolated from Purkinje cells and differential expression analysis was performed.
2024-01-01 | GSE223879 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-01-01 | GSE223881 | GEO
Project description:RNA-sequencing of Rreb1+/+ and Rreb1-/- embryonic day 7.5 mouse embryos
2021-04-21 | GSE148514 | GEO
Project description:RNA-sequencing of Rreb1+/+ and Rreb1-/- embryonic day 7.5 mouse embryos
| PRJNA624861 | ENA
Project description:Insulin-stimulated glucose uptake is known to involve microtubules, although the function of microtubules and the microtubule-regulating proteins involved in insulin action are poorly understood. CLASP2, a plus-end tracking microtubule-associated protein (+TIP) that controls microtubule dynamics, was recently implicated as the first +TIP associated with insulin-regulated glucose uptake. Here, using protein-specific targeted quantitative phosphoproteomics within 3T3-L1 adipocytes, we discovered that insulin regulates phosphorylation of the CLASP2 network members G2L1, MARK2, CLIP2, AGAP3 and CKAP5 as well as EB1, revealing the existence of a previously unknown microtubule-associated protein system that responds to insulin. To further investigate, G2L1 interactome studies within 3T3-L1 adipocytes revealed that G2L1 co-immunoprecipitates CLASP2 and CLIP2 as well as the master integrators of +TIP assembly, the end binding (EB) proteins. Live-cell total internal reflection fluorescence microscopy in adipocytes revealed G2L1 and CLASP2 colocalize on microtubule plus-ends. We found that while insulin increases the number of CLASP2-containing plus-ends, insulin treatment simultaneously decreases CLASP2-containing plus-end velocity. In addition, we discovered that insulin stimulates re-distribution of CLASP2 and G2L1 from exclusive plus-end tracking to “trailing” behind the growing tip of the microtubule. Insulin treatment increases -tubulin Lysine 40 acetylation, a mechanism that was observed to be regulated by a counterbalance between GSK3 and mTOR, and also led to microtubule stabilization. Our studies introduce insulin-stimulated microtubule stabilization and plus-end trailing of +TIPs as new modes of insulin action and reveal the likelihood that a network of microtubule-associated proteins synergize to coordinate insulin-regulated microtubule dynamics.
2019-06-13 | PXD011431 | Pride
Project description:RREB1 is an epigenetic regulator of the RAS-MAPK pathway genes.
2020-03-13 | GSE146902 | GEO
Project description:Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed EwS cases had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer, and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential, and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation.
2023-10-23 | GSE220780 | GEO
Project description:Buffering of deleterious mutations by molecular chaperones and degradation of aberrant proteins by quality control systems are both major factors that can impact the mutational landscape available to a client protein. The impacts of the proteostasis network on protein evolution are not limited to just endogenous clients, but can also shape the mutational landscapes accessible to rapidly evolving viral proteins. Here, we test the hypothesis that the composition of the host cell’s endoplasmic reticulum (ER) proteostasis network shapes the evolution of RNA viruses by focusing on human immunodeficiency virus-1 envelope (Env), a membrane glycoprotein that folds and matures in the host cell’s secretory pathway. We apply chemical genetic methods to activate the IRE1-XBP1s and/or the ATF6 transcriptional arms of the unfolded protein response in a stress-independent manner. We then quantitatively assess the impact of the resulting altered host cell ER proteostasis environments on the relative enrichment of all Env single amino acid substitutions using deep mutational scanning. We find that upregulation of host ER proteostasis factors globally reduces the mutational tolerance of HIV-1 Env, particularly upon induction of the IRE1-XBP1s transcriptional arm of the UPR. The effects of ATF6 activation are less global, but still significant at particular Env sites. The impact of the XBP1s-induced ER proteostasis environment is disparate for diverse structural elements of Env. Conserved, functionally important regions generally exhibit the largest decreases in mutational tolerance upon XBP1s activation. In contrast, specific regions of Env, including regions targeted by broadly neutralizing antibodies, display greatly enhanced mutational tolerance when XBP1s is activated. Altogether, these data reveal a new set of host factors that specifically shape the mutational space accessible to HIV Env and, more generally, provide compelling evidence that UPR-regulated proteostasis mechanisms play critical roles in membrane protein evolution.
2022-01-30 | GSE171356 | GEO
Project description:Epithelial-to-mesenchymal transitions (EMT) play prominent roles during development, regeneration and tumor progression. EMTs are triggered by TGF-β, RAS and other signals that cooperatively induce the expression of master EMT transcription factors such as SNAIL. Here, we elucidate how the TGF-β and RAS pathways jointly trigger EMTs and tie them to broader developmental programs. We identify RAS response element binding protein 1 (RREB1) as a critical partner of TGF-β-activated SMAD transcription factors in driving SNAIL expression in pancreatic pre-malignant epithelial cells, lung adenocarcinoma cells, and embryonic stem cells. Moreover, SMADs and RREB1 also drive EMT-associated fibrogenic programs in epithelial cells and mesendoderm differentiation in pluripotent embryonic cells. These findings illuminate the orchestration of EMT associated programs in gastrulation, fibrosis, and cancer.
2020-01-09 | GSE118765 | GEO
Project description:Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. Comprehensive transcriptome analysis was employed to validate the capacity of three prioritized compounds to remodel the ER proteostasis environment, and to assess the prefential activation of ATF6 transcriptional targets relative to targets of the IRE1/XBP1s and PERK arms of the UPR. HEK293T-Rex and HEK293-DAX cells were treated for 6 hr with vehicle (DMSO), 1 µM Tg, 10 mM TMP (in HEK293DAX), or 10 µM 132, 147 or 263 in biological triplicate at 37 ÌC
2016-07-21 | E-GEOD-84636 | biostudies-arrayexpress