Proteomic profiling of DLAT-interacting proteins in cisplatin-resistant lung cancer cells
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cell Culture
DISEASE(S): Lung Cancer
SUBMITTER: 
Jung Seok Hwang
LAB HEAD: Sumiin Kang
PROVIDER: PXD064757 | Pride | 2025-08-04
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| 68834_67316.mzXML | Mzxml | |||
| 68834_87987.mzid | Mzid | |||
| 68834_out.tgz | Other | |||
| 68834_sequest.params | Other | |||
| 68834_sequest_indexed.params | Other |
Items per page: 5 1 - 5 of 13 |
Similar Datasets
Project description:CpG-islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 possesses an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. Absence of SAMD1 impairs ES cell differentiation processes, leading to mis-regulation of key biological pathways. Together, our work establishes SAMD1 as a novel chromatin regulator acting at unmethylated CGIs.
2021-05-13 | PXD016781 | Pride
Project description:Mitochondrial oxidative phosphorylation (OXPHOS) complexes are assembled from proteins encoded by both nuclear and mitochondrial DNA. These dual-origin enzymes pose a complex gene regulatory challenge for cells requiring coordinated gene expression across organelles. To identify genes involved in dual-origin protein complex synthesis, we performed FACS-based genome-wide screens analyzing mutant cells with unbalanced levels of mitochondrial- and nuclear-encoded subunits of Complex IV. We identified novel genes involved in OXPHOS biogenesis, including two uncharacterized genes: PREPL and NME6. We found that PREPL specifically impacts Complex IV biogenesis by acting at the intersection of mitochondrial lipid metabolism and protein synthesis, while NME6, an uncharacterized nucleoside diphosphate kinase (NDPK), controls OXPHOS biogenesis through multiple mechanisms reliant on its NDPK domain. First, NME6 forms a complex with RCC1L, which together perform NDPK activity to maintain local mitochondrial pyrimidine triphosphate levels essential for mitochondrial RNA abundance. Second, NME6 modulates the activity of mitoribosome regulatory complexes, altering mitoribosome assembly and mitochondrial RNA pseudouridylation. Taken together, we propose that NME6 acts as a link between compartmentalized mitochondrial metabolites and mitochondrial gene expression.
2023-08-23 | PXD044812 | Pride
Project description:Aldehyde dehydrogenase 7A1 (ALDH7A1) is a metabolic enzyme that converts aldehydes to carboxylates. Here, we find that the reductive consequence of this catalytic activity, which generates NADH (nicotinamide adenine dinucleotide, reduced form) from NAD (nicotinamide adenine dinucleotide), underlies how ALDH7A1 coordinates a broad inhibition of the intracellular transport pathways. Studying vesicle formation by the Coat Protein I (COPI) complex, we elucidate that NADH generated by ALDH7A1 targets Brefeldin-A ADP-Ribosylated Substrate (BARS) to inhibit the fission stage. Moreover, defining a physiologic role for the broad transport inhibition exerted by ALDH7A1, we find that it acts to reduce energy consumption during hypoxia and starvation to promote cellular energy homeostasis. These findings uncover a non-canonical function of ALDH7A1, and also an unexpected way that NADH acts in cellular energetics. Moreover, the findings advance the understanding of intracellular transport by elucidating how multiple pathways can be coordinated, as well as defining physiologic circumstances in which this coordination occurs.
2019-09-12 | PXD014645 | Pride
Project description:The whole-cell scale spatial organization of lysosomes is regulated by their bidirectional motility on microtubule tracks. Small GTP-binding (G) protein, Arl8b, stimulates the anterograde transport of lysosomes by recruiting adaptor protein SKIP (also known as PLEKHM2), which in turn couples the microtubule motor kinesin-1. Here, we have identified an Arl8b effector, RUN and FYVE domaincontaining protein family member 3, RUFY3, which drives the retrograde transport of lysosomes. Artificial targeting of RUFY3 to the surface of mitochondria was sufficient to drive their perinuclear positioning. We find that RUFY3 interacts with the JIP4-Dynein-Dynactin complex and mediates Arl8b association with the retrograde motor complex. The mobile fraction of the total lysosomes per cell was significantly enhanced upon RUFY3 depletion, suggesting that RUFY3 maintains the lysosomes clustering within the perinuclear cloud. Expectedly, RUFY3 knockdown disrupted the perinuclear positioning of lysosomes upon nutrient starvation and/or serum depletion, although lysosome continued to undergo fusion with autophagosomes. Interestingly, lysosome fission events were more frequent in RUFY3-depleted cells and accordingly, there was a striking reduction in lysosome size, an effect that was also observed
2022-03-23 | PXD027010 | Pride
Project description:To identify novel regulators of the Hippo pathway, we performed affinity purification-mass spectrometry (AP-MS) using Drosophila embryos overexpressing Yki-EGFP with a ubiquitous driver da-GAL4, as well as cultured S2 cells expressing Yki-SBP. We identified the core Hippo pathway components, multiple Hippo pathway regulators and functional groups, and several putative Yki interactors including Bonus (Bon). To identify additional cofactors that are recruited by Bon, we performed AP-MS using Bon-SBP expressed in Drosophila S2 cells. Further genetic tests revealed the involvement of Bon interactors, HDAC1, Su(var)2-10, and Hrb27C, in the Drosophila eye specification that is regulated by the Yki-Bon complex.
2023-01-17 | PXD027934 | Pride
Project description:Using affinity purification-mass spectrometry (AP-MS), we identified the novel Mnb binding partners Ral interacting protein (Rlip) and RALBP1 associated Eps domain containing (Reps). Rlip and Reps physically and genetically interact with Mnb, and the three proteins may form a ternary complex. Mnb phosphorylates Reps, and human DYRK1A binds to the Reps orthologs REPS1 and REPS2. Furthermore, Mnb engages the small GTPase Ras-like protein A (Rala) to regulate brain and wing development. This work uncovers a previously unrecognized early role of Mnb in the neuroepithelium and defines the functions of the Mnb/Reps/Rlip/Rala signaling network in brain development.
2024-09-09 | PXD052378 | Pride
Project description:Very little is known about how animals discriminate pathogens from innocuous microbes. To address this question, we examined infection-response gene induction in the nematode Caenorhabditis elegans. We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but are not induced by an isogenic attenuated gacA mutant. Most of these genes are induced independently of known immunity pathways. We generated a GFP reporter for one of these genes, infection response gene 1 (irg-1), which is induced strongly by wild-type P. aeruginosa strain PA14, but not by other C. elegans pathogens or by other wild-type P. aeruginosa strains that are weakly pathogenic to C. elegans. To identify components of the pathway that induces irg-1 in response to infection, we performed an RNA interference screen of C. elegans transcription factors. This screen identified zip-2, a bZIP transcription factor that is required for inducing irg-1, as well as several other genes, and is important for defense against infection by P. aeruginosa. These data indicate that zip-2 is part of a specialized pathogen response pathway that is induced by virulent strains of P. aeruginosa and provides defense against this pathogen. Analysis of differential gene expression in adult N2 C. elegans treated with L4440 control RNAi or zip-2 RNAi, either uninfected (feeding on E. coli) or infected with P. aeruginosa PA14; samples were analyzed after 4 hours of infection
2013-08-30 | E-GEOD-50513 | biostudies-arrayexpress
Project description:Neuronal activity is critical for adaptive circuit remodeling but poses an inherent risk to the stability of the genome across the long lifespan of post-mitotic neurons1-5. Whether neurons have acquired specialized genome protection mechanisms that enable them to withstand decades of potentially damaging stimuli during periods of heightened activity is not known. Here we identify an activity-dependent DNA repair mechanism via a new form of the NuA4/TIP60 chromatin modifier that assembles in activated neurons around the inducible, neuronal-specific transcription factor NPAS4. We purify this complex directly from the brain and demonstrate its functions in eliciting activity-dependent changes to neuronal transcriptomes and circuitry. By identifying the landscape of activity-induced DNA double-strand breaks in the brain, we show that the NPAS4:NuA4 complex binds to recurrently damaged regulatory elements and recruits additional DNA repair machinery to stimulate their repair. Gene regulatory elements bound by the NPAS4:NuA4 complex are partially protected from age-dependent accumulation of somatic mutations. Impaired NPAS4:NuA4 signaling leads to a cascade of cellular defects including dysregulated transcriptional responses to activity, loss of control over neuronal inhibition, and genome instability, culminating in reduced organismal lifespan. In addition, mutations in several components of the NuA4 complex are reported to lead to neurodevelopmental disorders and autism. Together, these findings identify a neuronal-specific complex that couples neuronal activity directly to genome preservation and whose disruption may contribute to developmental disorders, neurodegeneration and aging.
2023-02-15 | PXD038718 | Pride
Project description:We overexpressed the spliced form of transcription factor XBP1 in mature F442A adipocytes by adenoviral infection. Control virus expressed GFP alone. mouse sXBP1 overexpressed in mouse F442A adipocytes compared to control (GFP alone). Four replicates of each treatment were analyzed.
2013-04-19 | E-GEOD-46178 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus in vitro with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 hours after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein; TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF-κB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-α in cells infected by the parental and mutant viruses indicated that activation of signaling by TNF-α is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-κB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-κB. The levels of CCL2 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF-κB signalling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF-B-dependent cytokine and chemokine release during HCMV infection , thereby impacting downstream immune responses.
2020-07-08 | PXD018328 | Pride