To comprehensively characterize the specificity of TP1 for HDAC4, we analyzed the effects of DMSO or TP1 via DIA proteomics analysis after lung cancer cells were treated with TP1 or DMSO
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Yi Sang
PROVIDER: PXD058069 | iProX | Tue Nov 19 00:00:00 GMT 2024
REPOSITORIES: iProX
Similar Datasets
Project description:We performed global gene expression analysis in mocetinostat- and DMSO-treated TC28a2 human chondrocyte cells, to study genes regulated by mocesinostat comprehensively.
2023-07-21 | GSE220755 | GEO
Project description:Bacterial small RNAs (sRNAs) are post-transcriptional regulators of stress response, virulence and more. The activity of sRNAs must be maintained across diverse environmental conditions, including the range of temperatures that defines the thermal niche of the species. Here we characterize the effects of temperature on the specificity and efficiency of sRNA regulation in E. coli. By measuring the activity of a large-scale library of sRNA variants at different temperatures, we found that many mutations have a significant but temperature-independent effect. We identified temperature-sensitive sequence elements using measurements that break from this dominant trend. Features associated with the specificity of sRNA regulation are more sensitive to mutations at high temperatures, and we confirm that specificity is more stringent at these temperatures. In contrast, many mutations in the region responsible for interactions with other targets have a stronger negative impact at low temperatures. Together, our results suggest that sRNAs may be structured such that variation in temperature may enhance their evolutionary plasticity.
2018-09-12 | GSE103732 | GEO
Project description:In this work, we used our recently developed method Spec-seq to characterize the binding specificity of Glucocorticoid receptor in vitro.
2015-07-01 | GSE69386 | GEO
Project description:A group of bacterial proteases, the Pro-Pro endopeptidases (PPEPs), possess the unique ability to hydrolyze proline-proline bonds in proteins. Since a protease’s function is largely determined by its substrate specificity, methods that can extensively characterize substrate specificity are valuable tools for protease research. Previously, we achieved an in-depth characterization of PPEP prime-side specificity. However, PPEP specificity is also determined by the non-prime-side residues in the substrate. To gain a more complete insight into the determinants of PPEP specificity, we characterized the non-prime- and prime-side specificity of various PPEPs using a combination of synthetic combinatorial peptide libraries and mass spectrometry. With this approach, we deepened our understanding of the P3-P3’ specificities of PPEP-1 and PPEP-2, while identifying PPEP-2’s endogenous substrate as the most optimal substrate in our library data. Furthermore, by employing the library approach, we investigated the altered specificity of mutants of PPEP-1 and PPEP-2. Additionally, we characterized a novel PPEP from Anoxybacillus tepidamans, which we termed PPEP-4. Based on structural comparisons, we hypothesized that PPEP-4 displays a PPEP-1-like prime-side specificity, which was substantiated by the experimental data. Intriguingly, another putative PPEP from Clostridioides difficile, CD1597, did not display Pro-Pro endoproteolytic activity. Collectively, we characterized PPEP specificity in detail using our robust peptide library method and, together with additional structural information, provide more insight into the intricate mechanisms that govern protease specificity.
2025-11-11 | PXD050236 | Pride
Project description:DMSO effect on HepaRG differentiation
| PRJNA439383 | ENA
Project description:In this study, we explored transcriptional complexity in human neutrophils, cells generally regarded as nonspecific in their functions and responses. We studied distinct human disease phenotypes and found that, at the gene, gene isoform, and miRNA level, neutrophils exhibit considerable specificity in their transcriptomes. These findings were particularly striking for isoform usage. Thus, even cells whose responses are considered non-specific show tailoring of their transcriptional repertoire toward specific physiologic or pathologic contexts. These findings have important implications for our understanding of the link between gene expression and disease phenotypes. Total RNA was extracted from isolated neutrophils from patients with JIA, from patients with cystic fibrosis and from healthy controls.
2015-09-18 | E-GEOD-71010 | biostudies-arrayexpress
Project description:Proteins function in crowded cellular environments in which they must bind to specific target proteins but also avoid binding to many other off-target proteins. In large protein families this task is particularly challenging because many off-target proteins have very similar structures. How this specificity of physical protein-protein interactions in cellular networks is encoded and evolves is not very well understood. Here we address the question of specificity-encoding by comprehensively quantifying the effects of all mutations in one protein, JUN, on its binding to all other members of a protein family, the 54 human basic leucine zipper transcription factors. Fitting a global thermodynamic model to the data reveals that most affinity changing mutations equally affect JUN’s propensity to bind to all its interaction partners. Mutations that alter the specificity of binding are much rarer. These specificity-altering mutations are, however, distributed throughout the JUN interaction interface. JUN’s interaction specificity is encoded by both positive determinants that promote on-target interactions and negative determinants that prevent off-target interactions. Indeed, about half of the specificity-defining residues in JUN have dual functions and both promote on-target binding and prevent off-target binding. Whereas nearly all mutations that alter specificity are pleiotropic and also alter the affinity of binding to all interaction partners, the converse is not true with mutations outside of the interface able to tune affinity without affecting specificity. Our results provide the first global view of how mutations in a protein affect binding to all its potential interaction partners and reveal the distributed encoding of specificity and affinity in an interaction interface. They also show how the modular architecture of coiled-coils provides an elegant solution to the challenge of optimising specificity and affinity in a large protein family.
2024-05-02 | GSE245326 | GEO
Project description:Interactions between RNAs and RNA binding proteins (RBPs) regulate gene expression in eukaryotic cells. RNA-RBP affinity measurements in vitro reveal diverse binding preferences, yet approaches to directly compare motif specificities across RBPs are lacking. Here, we introduce two quantitative metrics: inherent specificity, which measures how selectively an RBP distinguishes its strongest binding motif from all possible motifs, and variation sensitivity, which assesses tolerance to single nucleotide variations within a preferred motif. Analyzing high-throughput sequencing datasets, we compared these metrics across 100 RBPs in vitro and 27 RBPs in cells, finding a strong correlation between in vitro and cellular measurements for RBPs that bind RNA independently of local structural context. Through RNA binding domain swap CLIP experiments between low-specificity RBM25 and high-specificity HNRNPC, we demonstrated that sequence specificity can be measurably transferred between protein contexts. Using these insights, we developed mathematical models to understand how inherent specificity and mutational sensitivity shape competitive RBP binding in ways not predicted by affinity alone. These models reveal that low-specificity RBPs can functionally enhance the specificity of high-specificity RBPs by occupying non-target sites. Overexpression of low-specificity RBM25 in cells recapitulates this effect, sharpening HNRNPC binding toward its preferred target motifs. Together, this work establishes inherent specificity and variation sensitivity as a quantitative basis for modeling how RBPs compete for RNA targets, complementing affinity-based descriptions of RNA-RBP interactions.
2026-04-03 | GSE326416 | GEO
Project description:The type II nuclear receptors (NRs) function as heterodimeric transcription factors with the retinoid X receptor (RXR) to regulate diverse biological processes in response to endogenous ligands and therapeutic drugs. DNA-binding specificity has been proposed as a primary mechanism for NR gene regulatory specificity. We use protein-binding microarrays (PBMs) to comprehensively analyze the DNA binding of 12 NR:RXRα heterodimers. We find more promiscuous NR-DNA binding than has been reported, challenging the view that NR binding specificity is defined by half-site spacing. We show that NRs bind DNA using two distinct modes, explaining widespread NR binding to half-sites in vivo. Finally, we show that the current models of NR specificity better reflect binding-site activity rather than binding-site affinity. Our rich dataset and revised NR binding models provide a framework for understanding NR regulatory specificity and will facilitate more accurate analyses of genomic datasets.
2019-01-12 | GSE124910 | GEO