Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1054321 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27277819_1.fastq.gz | Fastqsanger.gz | |||
| SRR27277819_2.fastq.gz | Fastqsanger.gz | |||
| SRR27277820_1.fastq.gz | Fastqsanger.gz | |||
| SRR27277820_2.fastq.gz | Fastqsanger.gz | |||
| SRR27277821_1.fastq.gz | Fastqsanger.gz |
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Project description:Given the importance of deregulated phosphoinositide (PI) signaling in leukemic hematopoiesis, genes coding for proteins that regulate PI metabolism may have significant and as yet unappreciated roles in leukemia. We performed a targeted knockdown screen of PI modulator genes in human AML cells and identified candidates required to sustain proliferation or prevent apoptosis. One of these, the lipid kinase phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP4K2A) regulates cellular levels of phosphatidylinositol-5-phosphate (PtsIns5P) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). We found PIP4K2A to be essential for the clonogenic and leukemia-initiating potential of human AML cells, and for the clonogenic potential of murine MLL-AF9 AML cells. Importantly, PIP4K2A is also required for the clonogenic potential of primary human AML cells. Its knockdown results in accumulation of the cyclin-dependent kinase inhibitors CDKN1A and CDKN1B, G1 cell cycle arrest and apoptosis. Both CDKN1A accumulation and apoptosis were partially dependent upon activation of the mTOR pathway. Critically, however, PIP4K2A knockdown in normal hematopoietic stem and progenitor cells, both murine and human, did not adversely impact either clonogenic or multilineage differentiation potential, indicating a selective dependency which we suggest may be the consequence of the regulation of different transcriptional programmes in normal versus malignant cells. Thus, PIP4K2A is a novel candidate therapeutic target in myeloid malignancy.
2014-03-13 | GSE54309 | GEO
Project description:Escherichia coli of the B2 phylotype reside in human and animal intestines. We addressed the questions which host cell processes were dysregulated by E. coli HlyA that can potentiate intestinal diseases. The colon carcinoma cell line Caco-2 was infected by HlyA+ E. coli. Cell polarity regulation was analyzed by live cell imaging for the localization of phosphatidylinositol-4,5-bisphosphate (PIP2) abundance in the plasma membrane. In Caco-2 monolayers, transepithelial electrical resistance was measured to determine barrier function. Cell morphologyproliferation and dissemination was assessed microscopically. Cell signaling and polarity regulation was analyzed by RNA-Seq.
2021-09-01 | GSE169213 | GEO
Project description:Ovarian carcinoma is a significant cause of death among all gynecologic malignancies. OCCC originates from endometriosis with recurrent somatic mutations, especially in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). To testify the key enrichment pathway of combination of GSK458 with As2O3 in OCCC therapy, we use RNA sequence of four therapy groups (Control group, As2O3 (1uM) monotherapy, GSK458 (0.1uM) monotherapy, As2O3 combined with GSK458 group for 48h) in TOV21G cell line.
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Project description:Voltage-gated Kv7.2 potassium channels regulate neuronal excitability. The gating of Kv7 channels is regulated by various mediators and neurotransmitters acting via G protein-coupled receptors; the underlying signalling cascades involve phosphatidylinositol-4,5-bisphosphate (PIP2), Ca2+/Calmodulin and phosphorylation. Recent studies have reported that PIP2 sensitivity of Kv7.2 channels is affected by two PTMs, phosphorylation and methylation, harboured in the PIP2 binding domains. Here this project aimed to update phosphorylation and methylation sites on Kv7.2 from heterologous cells, the rat brain and GST-fusion Kv7.2 N- and C-terminal ends proteins.
2017-08-25 | PXD005567 | Pride
Project description:Given the importance of deregulated phosphoinositide (PI) signaling in leukemic hematopoiesis, genes coding for proteins that regulate PI metabolism may have significant and as yet unappreciated roles in leukemia. We performed a targeted knockdown screen of PI modulator genes in human AML cells and identified candidates required to sustain proliferation or prevent apoptosis. One of these, the lipid kinase phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP4K2A) regulates cellular levels of phosphatidylinositol-5-phosphate (PtsIns5P) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). We found PIP4K2A to be essential for the clonogenic and leukemia-initiating potential of human AML cells, and for the clonogenic potential of murine MLL-AF9 AML cells. Importantly, PIP4K2A is also required for the clonogenic potential of primary human AML cells. Its knockdown results in accumulation of the cyclin-dependent kinase inhibitors CDKN1A and CDKN1B, G1 cell cycle arrest and apoptosis. Both CDKN1A accumulation and apoptosis were partially dependent upon activation of the mTOR pathway. Critically, however, PIP4K2A knockdown in normal hematopoietic stem and progenitor cells, both murine and human, did not adversely impact either clonogenic or multilineage differentiation potential, indicating a selective dependency which we suggest may be the consequence of the regulation of different transcriptional programmes in normal versus malignant cells. Thus, PIP4K2A is a novel candidate therapeutic target in myeloid malignancy. AIM: to determine the transcriptional consequences of Pip4ka knockdown in murine normal and leukaemic bone marrow stem and progenitor cells. KIT+ stem and progenitor cells were immunomagnetically recovered from the bone marrow of two female C57/BL6 mice, pooled and cultured in RPMI with 20% FBS supplemented with SCF 300ng/mL, FL 1ng/mL and IL-11 20ng/mL. Next day these cells were spinfected with lentiviral supernatant (shPip4k2a constructs #1, #2 or a non-targeting control). Likewise, the same viral supernatant was used to spinfect (cryopreserved, thawed and overnight cultured) leukemic blasts recovered from the BM of mice with MLL-AF9 AML (initiated using a retroviral transduction and transplantation approach). Cells were FACS purified for GFP expression (the selectable marker) 48h following lentiviral infection and returned to culture. Seventy-two hours following lentiviral infection control and Pip4k2a KD cells were recovered from culture for mRNA extraction.
2014-03-13 | E-GEOD-54309 | biostudies-arrayexpress
Project description:While thousands of previously unannotated small and alternative open reading frames (alt-ORFs) have recently been revealed in the human genome, the functions of only a handful are currently known, leaving open the question of their biological significance as a class. Using a proteomic strategy for discovery of unannotated short open reading frames in human cells, we report the detection of alt-RPL36, a 148-amino acid protein co-encoded with and overlapping human RPL36. Alt-RPL36 interacts with TMEM24, which transports the phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] precursor phosphatidylinositol from the endoplasmic reticulum to the plasma membrane. Knock-out of alt-RPL36 in HEK 293T cells increased PI(4,5)P2 levels in the plasma membrane and upregulated the PI3K-AKT-mTOR signaling pathway. Remarkably, we find that four serine residues of alt-RPL36 are phosphorylated, and mutation of these four serines to alanine abolished the interaction with TMEM24 and regulation of PI3K signaling. These results implicate alt-RPL36 as a novel regulator of PI(4,5)P2 synthesis upstream of the PI3K-AKT-mTOR signaling pathway, and the first example of a phosphorylated alt-ORF product. More broadly, both alt-RPL36 and RPL36 regulate protein synthesis and cell growth via different molecular mechanisms – AKT signaling and ribosome composition, respectively. One human transcript can therefore express two sequence-independent polypeptides from overlapping ORFs that regulate the same processes via distinct mechanisms.
2020-12-07 | PXD018268 | Pride
Project description:Phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) is a lipid second messenger produced by class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2). Although typically associated with the plasma membrane, it is now appreciated that PI(3,4,5)P3 generation also occurs in the nucleus to regulate a variety of biological functions. Using a PI(3,4,5)P3-specific GST-GRP1PH domain reporter and immunofluorescence microscopy, we have found that DLD1 and SW480 colorectal cancer (CRC) cells exhibit pronounced nuclear staining of PI(3,4,5)P3. To characterise the nuclear PI(3,4,5)P3 interactome in DLD1 and SW480 cells, we performed affinity pull-down experiments on nuclear extracts using a ω-amino analogue of phosphatidylinositol 3,4,5 -triphosphate (PI(3,4,5)P3 immobilised onto Affi-gel10 beads. Gel fractionation and LC/MS-MS analysis was performed to reduce sample complexity and increase resolution, with samples run on a LTQ Orbitrap Elite mass spectrometer. DLD1 and SW480 cells were both analysed in four independent biological replicates. A protein was considered a member of the nuclear PI(3,4,5)P3 interactome if it was identified in at least two experiments (with at least two peptides, FDR of 1%) in both cell lines, yielding a total of 1237 unique proteins (representing 1103 genes for DLD1 and 1001 genes for SW480 cells).
2023-05-10 | PXD021936 | Pride
Project description:Conversion between phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate on endosomal membranes is critical for maturation of early endosomes to late endosomes/lysosomes, and is regulated by the PIKfyve-Vac14-Fig4 complex. In this study, we screened for the cellular interactome of Vac14 and Fig4 using proximity-dependent biotin labelling (BioID) in 293T cells.
2021-11-03 | PXD027917 | Pride
Project description:This data was performed as part of Revu et al, "Human IL-17A protein expression is controlled through a PIP5K1a-dependent ARS2 checkpoint". IL-17 secreted by TH17 cells is beneficial for microbial control, but causes inflammation and pathological tissue remodeling in autoimmunity. Hence TH17 differentiation and IL-17 production must be tightly regulated, but to date this has been defined only in terms of transcriptional control. Phosphatidyinositols are second messengers activated during T cell activation that transduce signals from the TCR and costimulatory receptors at the cell membrane. Here we show phosphatidylinositol(4,5)bisphosphate (PIP2) was unexpectedly enriched in the nucleus of human TH17 cells, dependent on the kinase PIP5K1, and that blockade of PIP5K1 impaired IL-17A production. In contrast, nuclear PIP2 enrichment was not observed in Th1 or Th2 cells and these subsets did not require PIP5K1 for cytokine production. In multiple sclerosis patient T cells, IL-17 production elicited by myelin basic protein could be inhibited by PIP5K1 blockade. Surprisingly, PIP5K1 blockade did not alter IL17A mRNA levels or stability in TH17 cells. Instead, analysis of PIP5K1-interacting proteins revealed that PIP5K1 targets ARS2, a nuclear cap binding complex scaffold protein, to facilitate ARS2 binding to IL17A mRNA and subsequent IL-17 protein expression, uncovering a new mechanism for regulating IL-17A protein production and suggesting a novel mechanism of translation control of cytokines.
2023-05-15 | GSE232436 | GEO
Project description:This a model from the article:
Metabotropic receptor activation, desensitization and sequestration-I: modelling
calcium and inositol 1,4,5-trisphosphate dynamics following receptor activation.
Lemon G, Gibson WG, Bennett MR. J Theor Biol
2003 Jul 7;223(1):93-111 12782119
,
Abstract:
A mathematical account is given of the processes governing the time courses of
calcium ions (Ca2+), inositol 1,4,5-trisphosphate (IP(3)) and
phosphatidylinositol 4,5-bisphosphate (PIP(2)) in single cells following the
application of external agonist to metabotropic receptors. A model is
constructed that incorporates the regulation of metabotropic receptor activity,
the G-protein cascade and the Ca2+ dynamics in the cytosol. It is subsequently
used to reproduce observations on the extent of desensitization and
sequestration of the P(2)Y(2) receptor following its activation by uridine
triphosphate (UTP). The theory predicts the dependence on agonist concentration
of the change in the number of receptors in the membrane as well as the time
course of disappearance of receptors from the plasmalemma, upon exposure to
agonist. In addition, the extent of activation and desensitization of the
receptor, using the calcium transients in cells initiated by exposure to
agonist, is also predicted. Model predictions show the significance of membrane
PIP(2) depletion and resupply on the time course of IP(3) and Ca2+ levels.
Results of the modelling also reveal the importance of receptor recycling and
PIP(2) resupply for maintaining Ca2+ and IP(3) levels during sustained
application of agonist.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Lemon G, Gibson WG, Bennett MR. (2003) - version=1.0
The original CellML model was created by:
Wei Liu
wliu052@aucklanduni.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230039 | BioModels