Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA808088 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18061303_1.fastq.gz | Fastqsanger.gz | |||
| SRR18061303_2.fastq.gz | Fastqsanger.gz | |||
| SRR18061304_1.fastq.gz | Fastqsanger.gz | |||
| SRR18061304_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Activated CD8+ T lymphocytes differentiate into heterogeneous subsets. Using super-resolution imaging, we found that prior to the first division, dynein-dependent vesicular transport polarized active TORC1 towards the microtubule-organizing center (MTOC) at the proximal pole. This active TORC1 was physically associated with active eIF4F, required for the translation of c-myc mRNA. As a consequence, c-myc translating polysomes polarized toward the cellular pole proximal to the immune synapse, resulting in localized c-myc translation. Upon division, the TORC1-eIF4A complex preferentially sorted to the proximal daughter cell, facilitating asymmetric c-Myc synthesis. Transient disruption of eIF4A activity at first division skewed long-term cell fate trajectories to memory-like function. Using a genetic barcoding approach, we found that first-division sister cells often displayed differences in transcriptional profiles that largely correlated with c-Myc and TORC1 target genes. Our findings provide mechanistic insights as to how distinct T cell fate trajectories can be established during the first division.
2022-04-24 | GSE196967 | GEO
Project description:Activated CD8+ T lymphocytes differentiate into heterogeneous subsets. Using super-resolution imaging, we found that prior to the first division, dynein-dependent vesicular transport polarized active TORC1 toward the microtubule-organizing center (MTOC) at the proximal pole. This active TORC1 was physically associated with active eIF4F, required for the translation of c-myc mRNA. As a consequence, c-myc-translating polysomes polarized toward the cellular pole proximal to the immune synapse, resulting in localized c-myc translation. Upon division, the TORC1-eIF4A complex preferentially sorted to the proximal daughter cell, facilitating asymmetric c-Myc synthesis. Transient disruption of eIF4A activity at first division skewed long-term cell fate trajectories to memory-like function. Using a genetic barcoding approach, we found that first-division sister cells often displayed differences in transcriptional profiles that largely correlated with c-Myc and TORC1 target genes. Our findings provide mechanistic insights as to how distinct T cell fate trajectories can be established during the first division.
| S-EPMC9271638 | biostudies-literature
Project description:Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray. Although most eukaryotic mRNAs need a functional cap binding complex eIF4F for efficient 5' end-dependent scanning to initiate translation, picornaviral, hepatitis C viral, and a few cellular RNAs have been shown to be translated by internal ribosome entry, a mechanism that can operate in the presence of low levels of functional eIF4F. To identify cellular mRNAs that can be translated when eIF4F is depleted or in low abundance and that, therefore, may contain internal ribosome entry sites, mRNAs that remained associated with polysomes were isolated from human cells after infection with poliovirus and were identified by using a cDNA microarray. Approximately 200 of the 7000 mRNAs analyzed remained associated with polysomes under these conditions. Among the gene products encoded by these polysome-associated mRNAs were immediate-early transcription factors, kinases, and phosphatases of the mitogen-activated protein kinase pathways and several protooncogenes, including c-myc and Pim-1. In addition, the mRNA encoding Cyr61, a secreted factor that can promote angiogenesis and tumor growth, was selectively mobilized into polysomes when eIF4F concentrations were reduced, although its overall abundance changed only slightly. Subsequent tests confirmed the presence of internal ribosome entry sites in the 5' noncoding regions of both Cyr61 and Pim-1 mRNAs. Overall, this study suggests that diverse mRNAs whose gene products have been implicated in a variety of stress responses, including inflammation, angiogenesis, and the response to serum, can use translational initiation mechanisms that require little or no intact cap binding protein complex eIF4F. This study is described more fully in Johannes G et al.(1999) Proc Natl Acad Sci U S A 96:13118-23.
2002-06-27 | E-GEOD-62 | biostudies-arrayexpress
Project description:To determine how TORC1 and PKA cooperate to regulate cell growth, we performed temporal analysis of gene expression in yeast switched from a non-fermentable substrate, to glucose, in the presence and absence of TORC1 and PKA inhibitors. Quantitative analysis of these data reveals that PKA drives the expression of key cell growth genes during transitions into, and out of, the rapid growth state in glucose, while TORC1 is important for the steady-state expression of the same genes.
2019-07-19 | GSE133591 | GEO
Project description:The Target Of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes regulate many different aspects of cell growth in response to intra- and extracellular cues. Here we report the first bona fide substrate of yeast TORC1: the AGC-kinase Sch9. Six amino acids in the c-terminus of Sch9 are directly phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin-treatment as well as carbon- or nitrogen-starvation and transiently reduced following application of osmotic, oxidative or thermal stress. TORC1-dependent phosphorylation is required for Sch9 activity and replacement of residues phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1-independent. Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation initiation and entry into G0 phase, but not expression of Gln3-dependent genes. Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt. Keywords: time course, cell type.
2007-04-28 | GSE7660 | GEO
Project description:Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray. Although most eukaryotic mRNAs need a functional cap binding complex eIF4F for efficient 5' end-dependent scanning to initiate translation, picornaviral, hepatitis C viral, and a few cellular RNAs have been shown to be translated by internal ribosome entry, a mechanism that can operate in the presence of low levels of functional eIF4F. To identify cellular mRNAs that can be translated when eIF4F is depleted or in low abundance and that, therefore, may contain internal ribosome entry sites, mRNAs that remained associated with polysomes were isolated from human cells after infection with poliovirus and were identified by using a cDNA microarray. Approximately 200 of the 7000 mRNAs analyzed remained associated with polysomes under these conditions. Among the gene products encoded by these polysome-associated mRNAs were immediate-early transcription factors, kinases, and phosphatases of the mitogen-activated protein kinase pathways and several protooncogenes, including c-myc and Pim-1. In addition, the mRNA encoding Cyr61, a secreted factor that can promote angiogenesis and tumor growth, was selectively mobilized into polysomes when eIF4F concentrations were reduced, although its overall abundance changed only slightly. Subsequent tests confirmed the presence of internal ribosome entry sites in the 5' noncoding regions of both Cyr61 and Pim-1 mRNAs. Overall, this study suggests that diverse mRNAs whose gene products have been implicated in a variety of stress responses, including inflammation, angiogenesis, and the response to serum, can use translational initiation mechanisms that require little or no intact cap binding protein complex eIF4F. This study is described more fully in Johannes G et al.(1999) Proc Natl Acad Sci U S A 96:13118-23. Keywords: other
2002-06-27 | GSE62 | GEO
Project description:The Target Of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes regulate many different aspects of cell growth in response to intra- and extracellular cues. Here we report the first bona fide substrate of yeast TORC1: the AGC-kinase Sch9. Six amino acids in the c-terminus of Sch9 are directly phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin-treatment as well as carbon- or nitrogen-starvation and transiently reduced following application of osmotic, oxidative or thermal stress. TORC1-dependent phosphorylation is required for Sch9 activity and replacement of residues phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1-independent. Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation initiation and entry into G0 phase, but not expression of Gln3-dependent genes. Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt. Keywords: time course, cell type. Global transcriptional analysis of rapamycin response was conducted on cells expressing either a wild-type, Sch9(WT), or TOR-independent allele of Sch9, Sch9(2D3E). Reference samples used were cells collected immediately prior to rapamycin treatment for the respective cell genotypes. Test samples were collected 20, 30, 60, 90, 120, and 180min post rapamycin treatment.
2010-09-15 | E-GEOD-7660 | biostudies-arrayexpress
Project description:Snf1 and TORC1 are two global regulators that sense the nutrient availability and regulate the cell growth in yeast Saccharomyces cerevisiae. Here we undertook a systems biology approach to study the effect of deletion of these genes and investigate the interaction between Snf1 and TORC1 in regulation of gene expression and cell metabolism.
2011-10-20 | GSE24421 | GEO
Project description:The eIF4F translation initiation complex plays a critical role in melanoma resistance to clinical BRAF and MEK inhibitors. In this study, we uncover a novel function of eIF4F in the negative regulation of the RAS/RAF/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway. We demonstrate that eIF4F is essential for maintaining optimal ERK signaling intensity in treatment-naïve melanoma cells harboring BRAF or NRAS mutations. Specifically, the dual-specificity phosphatase DUSP6/MKP3, which acts as a negative feedback regulator of ERK activity, requires continuous production in an eIF4F-dependent manner to limit excessive ERK signaling driven by oncogenic RAF/RAS mutations. Treatment with small molecule eIF4F inhibitors disrupts the negative feedback control of MAPK signaling, leading to ERK hyperactivation and EGR1 overexpression in melanoma cells in vitro and in vivo. Furthermore, our quantitative analyses reveal a high spare signaling capacity in the ERK pathway, suggesting that eIF4F-dependent feedback keeps the majority of ERK molecules inactive under normal conditions. Overall, our findings highlight the crucial role of eIF4F in regulating ERK signaling flux and suggest that pharmacological eIF4F inhibitors can disrupt the negative feedback control of MAPK activity in melanomas with BRAF and NRAS activating mutations.
2024-10-04 | GSE273721 | GEO