LIVIVO - Search results -

Search results

Result 1 - 10 of total 20

Search options

Article ; Online: Clonal transcriptomics identifies mechanisms of chemoresistance and empowers rational design of combination therapies.

Wild, Sophia A / Cannell, Ian G / Nicholls, Ashley / Kania, Katarzyna / Bressan, Dario / Hannon, Gregory J / Sawicka, Kirsty

eLife

2022 Volume 11

Abstract: Tumour heterogeneity is thought to be a major barrier to successful cancer treatment due to the presence of drug resistant clonal lineages. However, identifying the characteristics of such lineages that underpin resistance to therapy has remained ... ...

Abstract	Tumour heterogeneity is thought to be a major barrier to successful cancer treatment due to the presence of drug resistant clonal lineages. However, identifying the characteristics of such lineages that underpin resistance to therapy has remained challenging. Here, we utilise clonal transcriptomics with WILD-seq;
MeSH term(s)	Humans ; Mice ; Animals ; Drug Resistance, Neoplasm/genetics ; Nuclear Proteins ; Transcriptome ; Asparagine ; Transcription Factors ; Triple Negative Breast Neoplasms/pathology ; Taxoids/pharmacology ; Taxoids/therapeutic use
Chemical Substances	Nuclear Proteins ; Asparagine (7006-34-0) ; Transcription Factors ; taxane (1605-68-1) ; Taxoids
Language	English
Publishing date	2022-12-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.80981
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: FOXC2 promotes vasculogenic mimicry and resistance to anti-angiogenic therapy.

Cannell, Ian G / Sawicka, Kirsty / Pearsall, Isabella / Wild, Sophia A / Deighton, Lauren / Pearsall, Sarah M / Lerda, Giulia / Joud, Fadwa / Khan, Showkhin / Bruna, Alejandra / Simpson, Kathryn L / Mulvey, Claire M / Nugent, Fiona / Qosaj, Fatime / Bressan, Dario / Dive, Caroline / Caldas, Carlos / Hannon, Gregory J

Cell reports

2023 Volume 42, Issue 8, Page(s) 112791

Abstract: Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood ... ...

Abstract	Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood vessels, and their presence is generally associated with poor patient prognosis. Here we show that the transcription factor, Foxc2, promotes VM in diverse solid tumor types by driving ectopic expression of endothelial genes in tumor cells, a process that is stimulated by hypoxia. VM-proficient tumors are resistant to anti-angiogenic therapy, and suppression of Foxc2 augments response. This work establishes co-option of an embryonic endothelial transcription factor by tumor cells as a key mechanism driving VM proclivity and motivates the search for VM-inhibitory agents that could form the basis of combination therapies with anti-angiogenics.
MeSH term(s)	Humans ; Neovascularization, Pathologic/metabolism ; Cell Line, Tumor ; Immunotherapy
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112791
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: CPEB3-dependent increase in GluA2 subunits impairs excitatory transmission onto inhibitory interneurons in a mouse model of fragile X.

Hwang, Jee-Yeon / Monday, Hannah R / Yan, Jingqi / Gompers, Andrea / Buxbaum, Adina R / Sawicka, Kirsty J / Singer, Robert H / Castillo, Pablo E / Zukin, R Suzanne

Cell reports

2022 Volume 39, Issue 10, Page(s) 110853

Abstract: Fragile X syndrome (FXS) is a leading cause of inherited intellectual disability and autism. Whereas dysregulated RNA translation in Fmr1 knockout (KO) mice, a model of FXS, is well studied, little is known about aberrant transcription. Using single- ... ...

Abstract	Fragile X syndrome (FXS) is a leading cause of inherited intellectual disability and autism. Whereas dysregulated RNA translation in Fmr1 knockout (KO) mice, a model of FXS, is well studied, little is known about aberrant transcription. Using single-molecule mRNA detection, we show that mRNA encoding the AMPAR subunit GluA2 (but not GluA1) is elevated in dendrites and at transcription sites of hippocampal neurons of Fmr1 KO mice, indicating elevated GluA2 transcription. We identify CPEB3, a protein implicated in memory consolidation, as an upstream effector critical to GluA2 mRNA expression in FXS. Increased GluA2 mRNA is translated into an increase in GluA2 subunits, a switch in synaptic AMPAR phenotype from GluA2-lacking, Ca
MeSH term(s)	Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism ; Fragile X Syndrome/genetics ; Interneurons/metabolism ; Mice ; Mice, Knockout ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/metabolism
Chemical Substances	Cpeb3 protein, mouse ; Fmr1 protein, mouse ; RNA, Messenger ; RNA-Binding Proteins ; Receptors, AMPA ; Receptors, N-Methyl-D-Aspartate ; Fragile X Mental Retardation Protein (139135-51-6)
Language	English
Publishing date	2022-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.110853
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Dysregulation of mTOR signaling in neuropsychiatric disorders: therapeutic implications.

Sawicka, Kirsty / Zukin, R Suzanne

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2011 Volume 37, Issue 1, Page(s) 305–306

MeSH term(s)	Animals ; Autistic Disorder/drug therapy ; Autistic Disorder/metabolism ; Fragile X Syndrome/drug therapy ; Fragile X Syndrome/metabolism ; Humans ; Mice ; Psychopharmacology/methods ; Signal Transduction/drug effects ; Signal Transduction/physiology ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/physiology
Chemical Substances	MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; mTOR protein, mouse (EC 2.7.1.1)
Language	English
Publishing date	2011-12-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/npp.2011.210
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2379: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons.

Hale, Caryn R / Sawicka, Kirsty / Mora, Kevin / Fak, John J / Kang, Jin Joo / Cutrim, Paula / Cialowicz, Katarzyna / Carroll, Thomas S / Darnell, Robert B

eLife

2021 Volume 10

Abstract: Neurons rely on translation of synaptic mRNAs in order to generate activity-dependent changes in plasticity. Here, we develop a strategy combining compartment-specific crosslinking immunoprecipitation (CLIP) and translating ribosome affinity purification ...

Abstract	Neurons rely on translation of synaptic mRNAs in order to generate activity-dependent changes in plasticity. Here, we develop a strategy combining compartment-specific crosslinking immunoprecipitation (CLIP) and translating ribosome affinity purification (TRAP) in conditionally tagged mice to precisely define the ribosome-bound dendritic transcriptome of CA1 pyramidal neurons. We identify CA1 dendritic transcripts with differentially localized mRNA isoforms generated by alternative polyadenylation and alternative splicing, including many that have altered protein-coding capacity. Among dendritic mRNAs, FMRP targets were found to be overrepresented. Cell-type-specific FMRP-CLIP and TRAP in microdissected CA1 neuropil revealed 383 dendritic FMRP targets and suggests that FMRP differentially regulates functionally distinct modules in CA1 dendrites and cell bodies. FMRP regulates ~15-20% of mRNAs encoding synaptic functions and 10% of chromatin modulators, in the dendrite and cell body, respectively. In the absence of FMRP, dendritic FMRP targets had increased ribosome association, consistent with a function for FMRP in synaptic translational repression. Conversely, downregulation of FMRP targets involved in chromatin regulation in cell bodies suggests a role for FMRP in stabilizing mRNAs containing stalled ribosomes in this compartment. Together, the data support a model in which FMRP regulates the translation and expression of synaptic and nuclear proteins within different compartments of a single neuronal cell type.
MeSH term(s)	Animals ; Cell Body/physiology ; Dendrites/physiology ; Female ; Fragile X Mental Retardation Protein/genetics ; Gene Expression Regulation ; Male ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity/physiology ; Pyramidal Cells/classification ; Pyramidal Cells/physiology ; RNA, Messenger/genetics ; Transcriptome
Chemical Substances	RNA, Messenger ; Fragile X Mental Retardation Protein (139135-51-6)
Language	English
Publishing date	2021-12-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.71892
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Elevated ERK/p90 ribosomal S6 kinase activity underlies audiogenic seizure susceptibility in fragile X mice.

Sawicka, Kirsty / Pyronneau, Alexander / Chao, Miranda / Bennett, Michael V L / Zukin, R Suzanne

Proceedings of the National Academy of Sciences of the United States of America

2016 Volume 113, Issue 41, Page(s) E6290–E6297

Abstract: Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and a leading genetic form of autism. The Fmr1 KO mouse, a model of FXS, exhibits elevated translation in the hippocampus and the cortex. ERK (extracellular signal- ... ...

Abstract	Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and a leading genetic form of autism. The Fmr1 KO mouse, a model of FXS, exhibits elevated translation in the hippocampus and the cortex. ERK (extracellular signal-regulated kinase) and mTOR (mechanistic target of rapamycin) signaling regulate protein synthesis by activating downstream targets critical to translation initiation and elongation and are known to contribute to hippocampal defects in fragile X. Here we show that the effect of loss of fragile X mental retardation protein (FMRP) on these pathways is brain region specific. In contrast to the hippocampus, ERK (but not mTOR) signaling is elevated in the neocortex of fragile X mice. Phosphorylation of ribosomal protein S6, typically a downstream target of mTOR, is elevated in the neocortex, despite normal mTOR activity. This is significant in that S6 phosphorylation facilitates translation, correlates with neuronal activation, and is altered in neurodevelopmental disorders. We show that in fragile X mice, S6 is regulated by ERK via the "alternative" S6 kinase p90-ribosomal S6 kinase (RSK), as evidenced by the site of elevated phosphorylation and the finding that ERK inhibition corrects elevated RSK and S6 activity. These findings indicate that signaling networks are altered in the neocortex of fragile X mice such that S6 phosphorylation receives aberrant input from ERK/RSK. Importantly, an RSK inhibitor reduces susceptibility to audiogenic seizures in fragile X mice. Our findings identify RSK as a therapeutic target for fragile X and suggest the therapeutic potential of drugs for the treatment of FXS may vary in a brain-region-specific manner.
MeSH term(s)	Animals ; Cerebral Cortex/metabolism ; Cerebral Cortex/physiopathology ; DNA-Binding Proteins/metabolism ; Disease Models, Animal ; Epilepsy, Reflex/drug therapy ; Epilepsy, Reflex/etiology ; Epilepsy, Reflex/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fragile X Mental Retardation Protein/genetics ; Fragile X Mental Retardation Protein/metabolism ; Fragile X Syndrome/complications ; Mice ; Mice, Knockout ; Neurons/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Ribosomal Protein S6 Kinases, 90-kDa/antagonists & inhibitors ; Ribosomal Protein S6 Kinases, 90-kDa/metabolism ; Seizures/etiology ; Seizures/metabolism ; Signal Transduction ; Synapses/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Transcription Factors/metabolism
Chemical Substances	DNA-Binding Proteins ; Elf4 protein, mouse ; Fmr1 protein, mouse ; Transcription Factors ; Fragile X Mental Retardation Protein (139135-51-6) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Ribosomal Protein S6 Kinases, 90-kDa (EC 2.7.11.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
Language	English
Publishing date	2016-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1610812113
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1148: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Effect of varying molecular weight of dextran on acrylic-derivatized dextran and concanavalin A glucose-responsive materials for closed-loop insulin delivery.

Sahota, Tarsem / Sawicka, Kirsty / Taylor, Joan / Tanna, Sangeeta

Drug development and industrial pharmacy

2011 Volume 37, Issue 3, Page(s) 351–358

Abstract: Aim: Dextran methacrylate (dex-MA) and concanavalin A (con A)-methacrylamide were photopolymerized to produce covalently cross-linked glucose-sensitive gels for the basis of an implantable closed-loop insulin delivery device.: Methods: The ... ...

Abstract	Aim: Dextran methacrylate (dex-MA) and concanavalin A (con A)-methacrylamide were photopolymerized to produce covalently cross-linked glucose-sensitive gels for the basis of an implantable closed-loop insulin delivery device. Methods: The viscoelastic properties of these polymerized gels were tested rheologically in the non-destructive oscillatory mode within the linear viscoelastic range at glucose concentrations between 0 and 5% (w/w). Results: For each cross-linked gel, as the glucose concentration was raised, a decrease in storage modulus, loss modulus and complex viscosity (compared at 1 Hz) was observed, indicating that these materials were glucose responsive. The higher molecular weight acrylic-derivatized dextrans [degree of substitution (DS) 3 and 8%] produced higher complex viscosities across the glucose concentration range. Conclusions: These studies coupled with in vitro diffusion experiments show that dex-MA of 70 kDa and DS (3%) was the optimum mass average molar mass to produce gels that show reduced component leach, glucose responsiveness, and insulin transport useful as part of a self-regulating insulin delivery device.
MeSH term(s)	Acrylamides/chemistry ; Concanavalin A/chemistry ; Dextrans/chemistry ; Diffusion ; Drug Delivery Systems ; Feedback, Physiological ; Gels ; Glucose/analysis ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/chemistry ; Hypoglycemic Agents/pharmacology ; Infusion Pumps, Implantable ; Insulin/administration & dosage ; Insulin/chemistry ; Methacrylates ; Molecular Weight ; Temperature ; Viscosity
Chemical Substances	Acrylamides ; Dextrans ; Gels ; Hypoglycemic Agents ; Insulin ; Methacrylates ; methacrylated dextran ; Concanavalin A (11028-71-0) ; Glucose (IY9XDZ35W2) ; methacrylamide (K67NG89J77)
Language	English
Publishing date	2011-01-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	751874-2
ISSN	1520-5762 ; 0363-9045
ISSN (online)	1520-5762
ISSN	0363-9045
DOI	10.3109/03639045.2010.513983
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1335: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares.

Orange, Dana E / Yao, Vicky / Sawicka, Kirsty / Fak, John / Frank, Mayu O / Parveen, Salina / Blachere, Nathalie E / Hale, Caryn / Zhang, Fan / Raychaudhuri, Soumya / Troyanskaya, Olga G / Darnell, Robert B

The New England journal of medicine

2020 Volume 383, Issue 3, Page(s) 218–228

Abstract: Background: Rheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown.: Methods: We established a clinical and technical protocol ... ...

Abstract	Background: Rheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown. Methods: We established a clinical and technical protocol for repeated home collection of blood in patients with rheumatoid arthritis to allow for longitudinal RNA sequencing (RNA-seq). Specimens were obtained from 364 time points during eight flares over a period of 4 years in our index patient, as well as from 235 time points during flares in three additional patients. We identified transcripts that were differentially expressed before flares and compared these with data from synovial single-cell RNA-seq. Flow cytometry and sorted-blood-cell RNA-seq in additional patients were used to validate the findings. Results: Consistent changes were observed in blood transcriptional profiles 1 to 2 weeks before a rheumatoid arthritis flare. B-cell activation was followed by expansion of circulating CD45-CD31-PDPN+ preinflammatory mesenchymal, or PRIME, cells in the blood from patients with rheumatoid arthritis; these cells shared features of inflammatory synovial fibroblasts. Levels of circulating PRIME cells decreased during flares in all 4 patients, and flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells in 19 additional patients with rheumatoid arthritis. Conclusions: Longitudinal genomic analysis of rheumatoid arthritis flares revealed PRIME cells in the blood during the period before a flare and suggested a model in which these cells become activated by B cells in the weeks before a flare and subsequently migrate out of the blood into the synovium. (Funded by the National Institutes of Health and others.).
MeSH term(s)	Adult ; Arthritis, Rheumatoid/blood ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/immunology ; B-Lymphocytes/physiology ; Female ; Fibroblasts/metabolism ; Flow Cytometry ; Gene Expression ; Humans ; Male ; Mesenchymal Stem Cells/metabolism ; Middle Aged ; Patient Acuity ; Sequence Analysis, RNA/methods ; Surveys and Questionnaires ; Symptom Flare Up ; Synovial Fluid/cytology
Language	English
Publishing date	2020-08-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMoa2004114
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.34: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: FMRP has a cell-type-specific role in CA1 pyramidal neurons to regulate autism-related transcripts and circadian memory.

Sawicka, Kirsty / Hale, Caryn R / Park, Christopher Y / Fak, John J / Gresack, Jodi E / Van Driesche, Sarah J / Kang, Jin Joo / Darnell, Jennifer C / Darnell, Robert B

eLife

2019 Volume 8

Abstract: Loss of the RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown how FMRP function varies across brain regions and cell types and how this contributes to disease ... ...

Abstract	Loss of the RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown how FMRP function varies across brain regions and cell types and how this contributes to disease pathophysiology. Here we use conditional tagging of FMRP and CLIP (FMRP cTag CLIP) to examine FMRP mRNA targets in hippocampal CA1 pyramidal neurons, a critical cell type for learning and memory relevant to FXS phenotypes. Integrating these data with analysis of ribosome-bound transcripts in these neurons revealed CA1-enriched binding of autism-relevant mRNAs, and CA1-specific regulation of transcripts encoding circadian proteins. This contrasted with different targets in cerebellar granule neurons, and was consistent with circadian defects in hippocampus-dependent memory in
MeSH term(s)	Animals ; Autistic Disorder/genetics ; Autistic Disorder/metabolism ; Autistic Disorder/physiopathology ; CA1 Region, Hippocampal/cytology ; CA1 Region, Hippocampal/metabolism ; Cerebellum/cytology ; Cerebellum/metabolism ; Circadian Clocks/genetics ; Circadian Clocks/physiology ; Disease Models, Animal ; Fragile X Mental Retardation Protein/genetics ; Fragile X Mental Retardation Protein/metabolism ; Fragile X Syndrome/genetics ; Fragile X Syndrome/metabolism ; Fragile X Syndrome/physiopathology ; Gene Expression Regulation ; Humans ; Memory Disorders/genetics ; Memory Disorders/metabolism ; Memory Disorders/physiopathology ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/metabolism ; Pyramidal Cells/metabolism
Chemical Substances	Fragile X Mental Retardation Protein (139135-51-6)
Language	English
Publishing date	2019-12-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.46919
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity.

Moore, Michael J / Blachere, Nathalie E / Fak, John J / Park, Christopher Y / Sawicka, Kirsty / Parveen, Salina / Zucker-Scharff, Ilana / Moltedo, Bruno / Rudensky, Alexander Y / Darnell, Robert B

eLife

2018 Volume 7

Abstract: Dynamic post-transcriptional control of RNA expression by RNA-binding proteins (RBPs) is critical during immune response. ZFP36 RBPs are prominent inflammatory regulators linked to autoimmunity and cancer, but functions in adaptive immunity are less ... ...

Abstract	Dynamic post-transcriptional control of RNA expression by RNA-binding proteins (RBPs) is critical during immune response. ZFP36 RBPs are prominent inflammatory regulators linked to autoimmunity and cancer, but functions in adaptive immunity are less clear. We used HITS-CLIP to define ZFP36 targets in mouse T cells, revealing unanticipated actions in regulating T-cell activation, proliferation, and effector functions. Transcriptome and ribosome profiling showed that ZFP36 represses mRNA target abundance and translation, notably through novel AU-rich sites in coding sequence. Functional studies revealed that ZFP36 regulates early T-cell activation kinetics cell autonomously, by attenuating activation marker expression, limiting T cell expansion, and promoting apoptosis. Strikingly, loss of ZFP36 in vivo accelerated T cell responses to acute viral infection and enhanced anti-viral immunity. These findings uncover a critical role for ZFP36 RBPs in restraining T cell expansion and effector functions, and suggest ZFP36 inhibition as a strategy to enhance immune-based therapies.
MeSH term(s)	Animals ; Antiviral Agents/metabolism ; Base Sequence ; Bone Marrow/virology ; CD4-Positive T-Lymphocytes/metabolism ; Cell Lineage ; Immunity ; Kinetics ; Lymphocyte Activation ; Lymphocytic choriomeningitis virus/physiology ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Biosynthesis ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Ribosomes/metabolism ; T-Lymphocytes/metabolism ; Transcriptome/genetics ; Tristetraprolin/genetics ; Tristetraprolin/metabolism
Chemical Substances	Antiviral Agents ; RNA, Messenger ; RNA-Binding Proteins ; Tristetraprolin ; Zfp36 protein, mouse
Language	English
Publishing date	2018-05-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.33057
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito