Unbiased identification of Pleiotrophin-interacting proteins in the brain
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Brain
SUBMITTER: 
Belinda Willard
LAB HEAD: Peng Zhang, Ph.D.
PROVIDER: PXD081065 | Pride | 2026-07-21
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| PTN_1.d.zip | Other | |||
| PTN_1.mzXML | Mzxml | |||
| PTN_10.d.zip | Other | |||
| PTN_10.mzXML | Mzxml | |||
| PTN_11.d.zip | Other |
Items per page: 5 1 - 5 of 54 |
Similar Datasets
Project description:Aberrant expression of sialic acid containing glycolipids, or gangliosides and their corresponding synthases have been associated with a variety of cancers. GM2-synthase,the enzyme responsible for the formation of a pro-tumorigenic ganglioside, GM2 is well reported to be overexpressed across various cancer tissues and cell lines. This over-expression of GM2-synthase has been linked with increased migration, invasion and epithelial to mesenchymal transition (EMT) as well as induction of a local and systemic host immune suppression in cancer. Despite only a handful of studies demonstrating an epigenetic mechanism underlying the transcriptional regulation of GM2-synthase gene, the detailed mechanism still remains unclear. Here we identified the total proteome associated with the GM2-synthase promoter through a modified CRISPR-dCas9 based proteome profiling approach by categorizing all the identified proteins leading to a detailed elucidation of the molecular drivers behind GM2-synthase transcription. While the previous study identified an acetylation-dependent de-repression of the transcription factor SP1 causing GM2-synthase activation, the underlying molecular mechanism driving its activation wasn’t clear. This study demonstrated that the histone acetyltransferase (HAT), p300 acts a pivotal factor which on one hand cause acetylation-mediated degradation of SP1, and on the other hand modulates SMAD2/4 to have a direct positive impact on GM2 synthase gene transcription. We identified p300 to have an activator role in GM2 synthase gene transcription through knock out, knock down and over-expression experiments. Furthermore, SP1 degradation, SMAD activation and their DNA binding patterns shows the important role of p300 on SP1 and SMAD complexes. Altogether we have identified SMAD2/4 as an activator complex, p300 as a positive regulator and uncovered a critical p300-SMAD-SP1 regulatory axis in GM2--synthase transcriptional regulation.
2026-03-27 | PXD065551 | Pride
Project description:Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with >50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure. Here, we present our initial proteomic study of variation in β-lactamase expression that occurs in CRAb with different β-lactam antibiotics. Briefly, drug resistance to Ab (ATCC 19606) was induced by the administration of various classes of β-lactam antibiotics, and the cell-free supernatant was isolated, concentrated, separated by SDS-PAGE, digested with trypsin, and identified by label-free LC-MS-based quantitative proteomics. Thirteen proteins were identified and evaluated using a 1789 sequence database of Ab β-lactamases from UniProt, the majority of which were Class C β-lactamases (≥80%). Importantly, different antibiotics, even those of the same class (e.g. penicillin and amoxicillin), induced non-equivalent responses comprising various isoforms of Class C and D serine-β-lactamases, resulting in unique resistomes. These results open the door to a new approach of analyzing and studying the problem of multi-drug resistance in bacteria that rely strongly on β-lactamase expression.
2023-07-20 | PXD042336 | Pride
Project description:The nonstructural protein 3 (Nsp3) of SARS-CoV-2 is a large, multi-domain protein that localizes to double-membrane vesicles (DMVs), the physical site where SARS-CoV-2 (and other coronaviruses) replicate inside mammalian cells. One of the domains of Nsp3 is PLpro (papain-like protease), which harbors enzymatic activities (i.e., protease, deubiquitinase, and deISGylase). To identify human cellular proteins that bind Nsp3, we performed LC-MS/MS analysis of affinity-purified Nsp3 from SARS‑CoV‑2–infected Caco-2 (human intestinal epithelial) cells. This dataset identified numerous Nsp3-interacting proteins that play key roles in various host cellular processes, including metabolism and innate immunity.
2026-05-05 | PXD068796 | Pride
Project description:Background: Extracellular matrix remodeling mechanisms are understudied in cardiac development and congenital heart defects. Two similar matrix-degrading metalloproteases, ADAMTS1 and ADAMTS5, are extensively co-expressed during mouse cardiac development. The mouse mutants of each have mild cardiac anomalies, but their combined genetic inactivation is precluded by tight linkage. We coupled Adamts1 inactivation with pharmacologic ADAMTS5 blockade to uncover stage-specific cooperative roles and mechanisms in mouse cardiac development. Methods: ADAMTS5 blockade was achieved in Adamts1 null mouse embryos using an activity-blocking monoclonal antibody during distinct developmental windows covering myocardial compaction or cardiac septation and outflow tract rotation. Synchrotron imaging, RNA in situ hybridization, immunofluorescence microscopy and electron microscopy were used to determine the impact on cardiac development and compared to Gpc6 and ADAMTS-cleavage resistant mouse mutants. Mass spectrometry-based N-terminomics was used to identify relevant substrates. Results: Combined inactivation of ADAMTS1 and ADAMTS5 prior to 12.5 days of gestation led to dramatic accumulation of versican-rich cardiac jelly and inhibited formation of compact and trabecular myocardium, which we also observed in mice with ADAMTS cleavage-resistant versican. Subsequently, combined knockout impaired outflow tract development and ventricular septal closure, generating a tetralogy of Fallot-like defect independently of versican proteolysis. N-terminomics of combined ADAMTS knockout and wild-type hearts identified a cleaved glypican-6 peptide only in the wild-type and showed that ADAMTS1 and ADAMTS5 each cleaved glypican-6. Paradoxically, ADAMTS1 and ADAMTS5 inactivated hearts lacked glypican-6 despite unaltered Gpc6 transcription. Gpc6-/- mice demonstrated similar rotational defects as the combined ADAMTS knockout and both had reduced Hedgehog signaling. Conclusions: ADAMTS1 and ADAMTS5 ensure proper cardiac development via cleavage of distinct proteoglycans, each with independent roles in cardiac development. Whereas versican clearance in cardiac jelly is required for proper ventricular cardiomyogenesis, glypican-6 cleavage may activate/stabilize this cell-surface proteoglycan which is required for Hedgehog signaling during outflow tract development.
2025-05-06 | PXD045868 | Pride
Project description:Approaches for the discovery of molecular glues remain limited. Here we report a phenotypic screening approach in which cytotoxins whose mechanisms require ubiquitination show gain of viability following pharmacological inhibition of the Ubiquitin-life modifier activating enzyme (UBA1/UAE). This approach revealed PRLX-93936 and BMS-214662 as molecular glues that directly target the E3 ligase TRIM21 to induce degradation of nucleoporin proteins and inhibit nuclear trafficking. The cytotoxicity of these agents correlates strongly with TRIM21 expression, suggesting re-evaluation of these clinically-tested agents in patients with TRIM21-high cancers. Relative to recently-disclosed TRIM21-targeting glues, PRLX-93936 and newly-synthesized analogs represent a distinct structural series, lack known cellular off-targets, and offer greatly enhanced potency. Additionally, we have elaborated PRLX-93936 to the first ‘TRIMTAC’ that uses wild-type TRIM21 to degrade a multimeric protein. Together our work creates new opportunities for targeted protein degradation and enables the design of additional TRIM21-targeting glues and TRIMTACs.
2025-06-17 | PXD062839 | Pride
Project description:Steap4, a highly expressed protein in adipose tissue, has been implicated in metabolic homeostasis. In this study, we generated adipocyte-specific Steap4-deficient mice and observed that Steap4 deficiency led to increased fat mass and severe insulin resistance in a high-fat diet model. Mass spectrometry analysis revealed two classes of Steap4 interactomes: mitochondrial proteins and proteins involved in spliceosome. RNA-seq analysis of white adipose tissue demonstrated that Steap4 deficiency altered RNA splicing patterns with enriched functions in mitochondria. While interactome and transcriptome data implicate a role of Steap4 in mitochondria, Steap4 deficiency indeed impaired mitochondrial respiratory chain complex activity resulting in mitochondrial dysfunction in white adipose tissue. Consistently, brown adipocyte-specific Steap4-deficient mice also showed impaired mitochondrial function, increased whitening of brown adipose tissue, reduced energy expenditure, and exacerbated insulin resistance under HFD conditions. Overall, our findings elucidate the critical role of Steap4 in regulating adipocyte thermogenesis and energy expenditure by modulating mitochondrial function.
2025-02-03 | PXD046997 | Pride
Project description:Interferon-stimulated gene 15 (ISG15) regulates diverse cellular processes, including antiviral immunity, through its conjugation to proteins (ISGylation). Several viruses, including SARS-CoV-2, reverse the process of protein ISGylation by encoding specialized enzymes harboring deISGylating enzymatic activity. The papain-like protease (PLpro), which is part of the nonstructural protein 3 (Nsp3) of SARS-CoV-2, antagonizes mammalian host innate defense pathways by removing ISG15 from certain cellular substrates. However, the full substrate landscape of Nsp3-PLpro’s deISGylating activity is unknown. Moreover, PLpro, as part of Nsp3, localizes to double-membrane vesicles (DMVs), the sites where coronaviruses replicate inside cells; thus, this unique subcellular localization of Nsp3-PLpro is expected to restrain its substrate specificity. Here, we expressed in human cells a SARS-CoV-2 Nsp3-4 fusion construct that produces mature Nsp3 and Nsp4 via PLpro-mediated autoprocessing and promotes DMV formation, followed by IFNα treatment to mimic an infected state. Cells expressing empty vector with or without IFNα treatment, as well as cells expressing Nsp3-4 without IFNα stimulation were included for comparison. LC-MS/MS analysis identified numerous substrates of PLpro-mediated deISGylation that play roles in several major biological processes, including innate immune signaling, translational control, RNA metabolism, and oxidative stress responses. This global ISGylome dataset provides novel insights into how ISGylation regulates host cells at the molecular level and, further, how SARS-CoV-2 Nsp3-PLpro-mediated deISGylation influences the host ISGylome.
2026-05-05 | PXD068808 | Pride
Project description:Opportunistic infections of the respiratory tract often succeed under a weakened immune response caused by an underlying illness or hospitalization. The human fungal pathogen, Cryptococcus neoformans, and the bacterial pathogen, Klebsiella pneumoniae, are both well-characterized microbes that cause severe infections within immunocompromised individuals. In this study, we simulate a concentration-dependent pulmonary coinfection of a bacterial and fungal pathogen, and profile the proteomic changes by DDA vs. DIA. Dual perspective profiling provides new insights into host defense regulation of infection and pathogenic mechanisms of invasion.
2024-08-13 | PXD054527 | Pride
Project description:Takotsubo syndrome is a stress-induced cardiomyopathy with symptoms comparable to those of acute coronary syndrome but without coronary obstruction. Initially considered spontaneously reversible, the reversibility of takotsubo was challenged by epidemiological studies showing high morbi-mortality in the long term. Here we explore comprehensively cardiac metabolism, structure and function after a single acute stress. We show that a single pharmacological stress is sufficient to recapitulate the clinical signs of ventricular dysfunction of takotsubo and their apparent reversibility. Interestingly, myocardial glucose metabolic remodeling during the acute phase was also present throughout the late recovery phases. Metabolic stunning where high glucose uptake is derived from glycolysis into alternative non-oxidative pathways such as the hexosamine biosynthetic and polyol pathways parallels with irreversible tissue and vascular remodeling. This study evidences that stress-induced diversion of glucose metabolism is the cause of deleterious structural and functional sequelae in takotsubo hearts.
2023-06-28 | PXD032667 | Pride
Project description:Cancer cells rely on mitochondria for their bioenergetic supply and macromolecule synthesis. Central to mitochondrial function is the regulation of mitochondrial protein synthesis, which primarily depends on the cytoplasmic translation of nuclear-encoded mitochondrial mRNAs whose protein products are imported into mitochondria. Despite the growing evidence that mitochondrial protein synthesis contributes to the onset and progression of cancer, and offers new opportunities for cancer therapy, knowledge of the underlying molecular mechanisms remains limited. Here, we show that RNA G-quadruplexes (RG4s) are co-localized with mitochondria and regulate mitochondrial function by modulating cytoplasmic mRNA translation of nuclear- encoded mitochondrial proteins. Our data support a model whereby the RG4 folding dynamics, under the control of oncogenic signaling and modulated by small molecule ligands or RG4-binding proteins, modifies mitochondria-localized cytoplasmic protein synthesis. Ultimately, this impairs mitochondrial functions, affecting energy metabolism and consequently cancer cell proliferation.
2025-05-06 | PXD046213 | Pride