Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1187288 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31372714.fastq.gz | Fastqsanger.gz | |||
| SRR31372714_1.fastq.gz | Fastqsanger.gz | |||
| SRR31372714_2.fastq.gz | Fastqsanger.gz | |||
| SRR31372715.fastq.gz | Fastqsanger.gz | |||
| SRR31372715_1.fastq.gz | Fastqsanger.gz |
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Project description:PTPN23-dependent ESCRT machinery functions as a cell death checkpoint in restraining multiple cell death pathways
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Project description:Cell death plasticity is crucial for modulating tissue homeostasis and immune responses, but our understanding of the molecular components that regulate cell death pathways to determine cell fate remains limited. Here, a CRISPR screen of acute myeloid leukemia cells identifies protein tyrosine phosphatase non-receptor type 23 (PTPN23) as essential for survival. Loss of PTPN23 activates nuclear factor-kappa B, apoptotic, necroptotic, and pyroptotic pathways by causing the accumulation of death receptors and toll-like receptors (TLRs) in endosomes. These effects are recapitulated by depletion of PTPN23 co-dependent genes in the endosomal sorting complex required for transport (ESCRT) pathway. Through proximity-dependent biotin labeling, we show that NAK-associated protein 1 interacts with PTPN23 to facilitate endosomal sorting of tumor necrosis factor receptor 1 (TNFR1), sensitizing cells to TNF-alpha-induced cytotoxicity. Our findings reveal PTPN23-dependent ESCRT machinery as a cell death checkpoint that regulates the spatiotemporal distribution of death receptors and TLRs to restrain multiple cell death pathways.
2024-10-16 | GSE272123 | GEO
Project description:In our study, a CRISPR screen of acute myeloid leukemia cells identifies protein tyrosine phosphatase non-receptor type 23 (PTPN23) as essential for survival. Loss of PTPN23 activates nuclear factor-kappa B, apoptotic, necroptotic, and pyroptotic pathways by causing the accumulation of death receptors and toll-like receptors (TLRs) in endosomes. These effects are recapitulated by depletion of PTPN23 co-dependent genes in the endosomal sorting complex required for transport (ESCRT) pathway. Through proximity-dependent biotin labeling, we show that NAK-associated protein 1 interacts with PTPN23 to facilitate endosomal sorting of tumor necrosis factor receptor 1 (TNFR1), sensitizing cells to TNF--induced cytotoxicity. Our findings reveal PTPN23-dependent ESCRT machinery as a cell death checkpoint that regulates the spatiotemporal distribution of death receptors and TLRs to restrain multiple cell death pathways.
2024-10-15 | PXD056836 |
Project description:The activation of Mixed Lineage Kinase-Like (MLKL) by Receptor Interacting Protein Kinase-3 (RIPK3) results in plasma membrane (PM) disruption and a form of regulated necrosis, called necroptosis. Here we show that during necroptosis, MLKL-dependent calcium (Ca++) influx and phosphatidylserine (PS) exposure on the outer leaflet of the plasma membrane preceded loss of PM integrity. Activation of MLKL results in the generation of broken, PM “bubbles” with exposed PS that are released from the surface of the otherwise intact cell. Components of the ESCRT machinery are required for formation of these bubbles, and act to sustain survival of the cell when MLKL activation is limited or reversed. Under conditions of necroptotic cell death, ESCRT controls the duration of plasma membrane integrity. As a consequence of the action of ESCRT, cells undergoing necroptosis can express chemokines and other regulatory molecules, and promote antigenic cross-priming of CD8+ T cells.
2017-06-16 | GSE85660 | GEO
Project description:Components of the ESCRT machinery act downstream of MLKL to regulate necroptotic cell death and its consequences
| PRJNA339009 | ENA
Project description:The ESCRT machinery drives the multivesicular body (MVB) pathway in eukaryotic cells and thus is required for the degradation of ubiquitinated membrane proteins in lysosomes. To systematically characterize how cells respond to loss of ESCRT function, we used quantitative proteomics and gene expression profiling in yeast. We find that ESCRT mutants display severe defects in amino acid homeostasis, resulting in lower levels of free intracellular amino acids. This deficit renders the growth of ESCRT mutants highly sensitive to nutrient limitation. Further proteomic analysis revealed that the MVB pathway essentially contributes to proteome remodeling under nutrient limitation. The rapid decline of protein synthesis upon starvation no longer enables ESCRT mutants to complete their cell cycle and properly enter a quiescent state, which strongly affects their long-term survival. Thus, the MVB pathway functions to selectively down-regulate integral membrane proteins and, together with autophagy and proteasomal degradation, considerably contributes to amino acid recycling. We used microarrays to identify gene expression changes between delta VPS4 knock out and wild type Saccharomyces cerevisiae strains
2018-01-01 | GSE53774 | GEO
Project description:Within the endolysosomal pathway in mammalian cells, ESCRT complexes facilitate degradation of membrane proteins from limiting membranes of late endosomes. Recent studies revealed that yeast ESCRT proteins also sort for degradation, ubiquitinated proteins from vacuolar membrane. However, whether mammalian ESCRTs perform similar function at lysosomes remained unknown. Here, we studied the involvement of mammalian ESCRT-I in maintaining lysosomal membrane homeostasis and its implication in lysosome-related signaling. We show that ESCRT-I restricts the size of lysosomes and promotes degradation of lysosomal Ca2+ channel, MCOLN1 protein. ESCRT-I depletion induced transcriptional response related to MiT-TFE signaling and cholesterol biosynthesis, pointing to lysosomal dysfunction. The lack of ESCRT-I promoted abnormal cholesterol accumulation on lysosomes and activated TFEB/TFE3 transcription factors in Ca2+-MCOLN1-dependent, but lipid-independent manner. Hence, our study provides evidence that ESCRT-I maintains lysosomal homeostasis and elucidates MiT-TFE regulatory mechanism activated in response to ESCRT-I deprivation
2022-03-28 | GSE178665 | GEO
Project description:The B cell-specific BACH2 transcription factor is required for affinity maturation of mature B cells. Here, we show that Bach2 mediates negative selection at the pre-B cell receptor checkpoint and functions as a critical safeguard against leukemogenesis. Bach2-mediated activation of p53 is required for stringent elimination of pre-B cells that failed to productively rearrange immunoglobulin VH-DJH gene segments, and thus lack pre-B cell receptor expression. Upon productive VH-DJH gene rearrangement, pre-B cell receptor signaling ends negative selection through BCL6-mediated repression of p53. In patients with pre-B acute lymphoblastic leukemia, Bach2-mediated checkpoint control is frequently compromised and low levels of Bach2 expression represent a strong independent predictor of poor clinical outcome. Bach2+/+ pre-B cells resist leukemic transformation by Myc through Bach2-dependent upregulation of p53. Upon transformation with Myc, Bach2-/- pre-B cells fail to upregulate p53, form large colonies and initiate fatal leukemia in transplant recipient mice. ChIP-seq and gene expression analyses revealed that BACH2 competes with BCL6 for promoter binding and reverses BCL6-mediated repression of p53 and multiple other checkpoint control genes. These findings identify Bach2 as a key activator of p53 in pre-B cells, which is critical to maintain stringency of the pre-B cell receptor checkpoint and an important barrier against leukemic transformation. ChIP-seq using BACH2 and BCL6 antibodies in OCI-Ly7 cells
2013-06-27 | E-GEOD-44420 | biostudies-arrayexpress
Project description:S100A8/A9 is a proinflammatory mediator released by myeloid cells during many acute and chronic inflammatory disorders. However, the precise mechanism of its release from the cytosolic compartment of neutrophils is still elusive. We report here that E-selectin-induced rapid S100A8/A9 release during inflammation occurs in a NLRP3 inflammasome-dependent fashion. Mechanistically, E-selectin engagement triggers Bruton?s tyrosine kinase dependent tyrosine phosphorylation of NLRP3. Concomitant potassium efflux via the voltage-gated potassium channel KV1.3 mediates ASC oligomerization. This is followed by caspase-1 cleavage and downstream activation of pore forming gasdermin D, enabling cytosolic S100A8/A9 to be released. Strikingly, E-selectin-mediated gasdermin D pore formation does not result in cell death, but is a transient process involving activation of the ESCRT-III membrane repair machinery. These findings do not only elucidate the molecular mechanisms of controlled S100A8/A9 release but also identify the NLRP3/gasdermin D axis as a rapid and reversible activation system in neutrophils during inflammation.
2023-10-25 | PXD041652 | Pride
Project description:Cytokinesis requires the constriction of ESCRT-III filaments on the midbody side, where abscission occurs. After ESCRT recruitment at the midbody, it is not known how the ESCRT-III machinery localizes to the abscission site. We obtained the proteome of intact, post-abscission midbodies (Flemmingsome) and revealed enriched proteins in this organelle. We propose that the ESCRT-III machinery must be physically coupled to a membrane protein at the cytokinetic abscission site for productive scission, revealing novel common requirements in cytokinesis, exosome formation and retroviral budding.
2020-05-22 | PXD013219 | Pride