Stress kinases in the modulation of metabolism and energy balance

Obesity is a new global pandemic, with growing incidence and prevalence. This disease is associated with increased risk of several pathologies, including diabetes, cardiovascular diseases, and cancer. The mechanisms underlying obesity-associated metabolic changes are the focus of efforts to identify new therapies. Stress-activated protein kinases (SAPK), including cJun N-terminal kinases (JNKs) and p38, are required for cellular responses to metabolic stress and therefore might contribute to the pathogenesis of obesity. Tissue-specific knockout models support a cell-type-specific role for JNK isoforms, in particular JNK1, highlighting its importance in cell homeostasis and organ crosstalk. However, more efforts are needed to elucidate the specific roles of other JNK isoforms and p38 family members in metabolism and obesity. This review provides an overview of the role of SAPKs in the regulation of metabolism.

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miR-27 and miR-125 Distinctly Regulate Muscle-Enriched Transcription Factors in Cardiac and Skeletal Myocytes

BioMed Research International ◽

10.1155/2015/391306 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

Estefania Lozano-Velasco ◽

Jennifer Galiano-Torres ◽

Alvaro Jodar-Garcia ◽

Amelia E. Aranega ◽

Diego Franco

Keyword(s):

Transcription Factors ◽

Cardiac Development ◽

Protein Translation ◽

Cell Type ◽

Atrial Cardiomyocytes ◽

Skeletal Myocytes ◽

Specific Manner ◽

A Cell ◽

Cell Type Specific

MicroRNAs are noncoding RNAs of approximately 22–24 nucleotides which are capable of interacting with the 3′ untranslated region of coding RNAs (mRNAs), leading to mRNA degradation and/or protein translation blockage. In recent years, differential microRNA expression in distinct cardiac development and disease contexts has been widely reported, yet the role of individual microRNAs in these settings remains largely unknown. We provide herein evidence of the role of miR-27 and miR-125 regulating distinct muscle-enriched transcription factors. Overexpression of miR-27 leads to impair expression ofMstnandMyocdin HL1 atrial cardiomyocytes but not in Sol8 skeletal muscle myoblasts, while overexpression of miR-125 resulted in selective upregulation ofMef2din HL1 atrial cardiomyocytes and downregulation in Sol8 cells. Taken together our data demonstrate that a single microRNA, that is, miR-27 or miR-125, can selectively upregulate and downregulate discrete number of target mRNAs in a cell-type specific manner.

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Faculty Opinions recommendation of Genetic deletion of SEPT7 reveals a cell type-specific role of septins in microtubule destabilization for the completion of cytokinesis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718529881.793499809 ◽

2014 ◽

Author(s):

Serge Mostowy ◽

Maria J Mazon-Moya

Keyword(s):

Specific Role ◽

Cell Type ◽

A Cell ◽

Cell Type Specific ◽

Genetic Deletion

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Genetic Deletion of SEPT7 Reveals a Cell Type-Specific Role of Septins in Microtubule Destabilization for the Completion of Cytokinesis

PLoS Genetics ◽

10.1371/journal.pgen.1004558 ◽

2014 ◽

Vol 10 (8) ◽

pp. e1004558 ◽

Cited By ~ 53

Author(s):

Manoj B. Menon ◽

Akihiro Sawada ◽

Anuhar Chaturvedi ◽

Pooja Mishra ◽

Karin Schuster-Gossler ◽

...

Keyword(s):

Specific Role ◽

Cell Type ◽

A Cell ◽

Cell Type Specific ◽

Genetic Deletion

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A Cell Type-Specific Role of Protein Tyrosine Phosphatase Non-Receptor Type 2 in Regulating ER Stress Signalling

Digestion ◽

10.1159/000375459 ◽

2015 ◽

Vol 91 (3) ◽

pp. 248-256 ◽

Cited By ~ 1

Author(s):

Stephanie H. Kasper ◽

Marianne R. Spalinger ◽

Tina Raselli ◽

Michael Scharl

Keyword(s):

Er Stress ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Specific Role ◽

Receptor Type ◽

Cell Type ◽

A Cell ◽

Cell Type Specific

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Amino termini of histones H3 and H4 are required for a1-alpha2 repression in yeast.

Molecular and Cellular Biology ◽

10.1128/mcb.17.11.6555 ◽

1997 ◽

Vol 17 (11) ◽

pp. 6555-6562 ◽

Cited By ~ 34

Author(s):

L Huang ◽

W Zhang ◽

S Y Roth

Keyword(s):

General Feature ◽

Amino Terminus ◽

Specific Gene ◽

Alpha Cells ◽

Histone H4 ◽

Cell Type ◽

A Cell ◽

Cell Type Specific ◽

Diploid Cells

The Saccharomyces cerevisiae alpha2 repressor controls two classes of cell-type-specific genes in yeast through association with different partners. alpha2-Mcm1 complexes repress a cell-specific gene expression in haploid alpha cells and diploid a/alpha cells, while a1-alpha2 complexes repress haploid-specific genes in diploid cells. In both cases, repression is mediated through Ssn6-Tu1 corepressor complexes that are recruited via direct interactions with alpha2. We have previously shown that nucleosomes are positioned adjacent to the alpha2-Mcm1 operator under conditions of repression and that Tupl interacts directly with histones H3 and H4. Here, we examine the role of chromatin in a1-alpha2 repression to determine if chromatin is a general feature of repression by Ssn6-Tup1. We find that mutations in the amino terminus of histone H4 cause a 4- to 11-fold derepression of a reporter gene under a1-alpha2 control, while truncation of the H3 amino terminus has a more modest (3-fold or less) effect. Strikingly, combination of the H3 truncation with an H4 mutation causes a 40-fold decrease in repression, clearly indicating a central role for these histones in a1-alpha2-mediated repression. However, in contrast to the ordered positioning of nucleosomes adjacent to the alpha2-Mcm1 operator, nucleosomes are not positioned adjacent to the a1-alpha2 operator in diploid cells. Our data indicate that chromatin is important to Ssn6-Tup1-mediated repression but that the degrees of chromatin organization directed by these proteins differ at different promoters.

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N-cadherin (Cdh2) Maintains Migration and Postmitotic Survival of Cortical Interneuron Precursors in a Cell-Type-Specific Manner

Cerebral Cortex ◽

10.1093/cercor/bhz168 ◽

2019 ◽

Vol 30 (3) ◽

pp. 1318-1329

Author(s):

Zsófia I László ◽

Kinga Bercsényi ◽

Mátyás Mayer ◽

Kornél Lefkovics ◽

Gábor Szabó ◽

...

Keyword(s):

Target Selection ◽

Cortical Plate ◽

Specific Factor ◽

Cell Type ◽

Cortical Interneuron ◽

Specific Manner ◽

A Cell ◽

Cell Type Specific ◽

Interneuron Development

Abstract The multiplex role of cadherin-based adhesion complexes during development of pallial excitatory neurons has been thoroughly characterized. In contrast, much less is known about their function during interneuron development. Here, we report that conditional removal of N-cadherin (Cdh2) from postmitotic neuroblasts of the subpallium results in a decreased number of Gad65-GFP-positive interneurons in the adult cortex. We also found that interneuron precursor migration into the pallium was already delayed at E14. Using immunohistochemistry and TUNEL assay in the embryonic subpallium, we excluded decreased mitosis and elevated cell death as possible sources of this defect. Moreover, by analyzing the interneuron composition of the adult somatosensory cortex, we uncovered an unexpected interneuron-type-specific defect caused by Cdh2-loss. This was not due to a fate-switch between interneuron populations or altered target selection during migration. Instead, potentially due to the migration delay, part of the precursors failed to enter the cortical plate and consequently got eliminated at early postnatal stages. In summary, our results indicate that Cdh2-mediated interactions are necessary for migration and survival during the postmitotic phase of interneuron development. Furthermore, we also propose that unlike in pallial glutamatergic cells, Cdh2 is not universal, rather a cell type-specific factor during this process.

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Chromatin accessibility determines intron retention in a cell type-specific manner

10.1101/2021.02.17.431609 ◽

2021 ◽

Author(s):

Veronika Petrova ◽

Renhua Song ◽

Karl J.V. Nordström ◽

Jörn Walter ◽

Justin J.-L. Wong ◽

...

Keyword(s):

Nucleosome Occupancy ◽

Intron Retention ◽

Chromatin Accessibility ◽

Lymphoid Cells ◽

Cell Type ◽

Systematic Analysis ◽

Specific Manner ◽

A Cell ◽

Cell Type Specific

SummaryDynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR is associated with numerous human diseases including cancer. Despite consistent reports demonstrating intrinsic sequence features that predispose introns to become retained, conflicting findings about cell type-specific IR regulation demand a systematic analysis in a controlled experimental setting. We integrated matched transcriptomics and epigenetics data (including DNA methylation, nucleosome occupancy, histone modifications) from primary human myeloid and lymphoid cells. Using machine learning we trained two complementary models to determine the role of epigenetic factors in the regulation of IR. We show that increased chromatin accessibility contributes substantially to the retention of introns in a cell-specific manner. We also confirm that intrinsic characteristics of introns are key for them to evade splicing. With mounting reports linking pathogenic alterations to RNA processing, our findings may have profound implications for the design of therapeutic approaches targeting aberrant splicing.

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