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Your search keyword '"Britta Fielitz"' showing total 2 results
Start Over Author "Britta Fielitz" Topic physiology
2 results on '"Britta Fielitz"'

1. Activation of Tripartite Motif Containing 63 Expression by Transcription Factor EB and Transcription Factor Binding to Immunoglobulin Heavy Chain Enhancer 3 Is Regulated by Protein Kinase D and Class IIa Histone Deacetylases

Author

Cristina Pablo Tortola, Britta Fielitz, Yi Li, Julia Rüdebusch, Friedrich C. Luft, and Jens Fielitz

Subjects
muscle atrophy, protein kinase D, HDAC = histone deacetylase, transcription factor EB, TFE3, muscle ring finger protein 1, Physiology, QP1-981
Abstract

RationaleThe ubiquitin–proteasome system (UPS) is responsible for skeletal muscle atrophy. We showed earlier that the transcription factor EB (TFEB) plays a role by increasing E3 ubiquitin ligase muscle really interesting new gene-finger 1(MuRF1)/tripartite motif-containing 63 (TRIM63) expression. MuRF 1 ubiquitinates structural proteins and mediates their UPS-dependent degradation. We now investigated how TFEB-mediated TRIM63 expression is regulated.ObjectiveBecause protein kinase D1 (PKD1), histone deacetylase 5 (HDAC5), and TFEB belong to respective families with close structural, regulatory, and functional properties, we hypothesized that these families comprise a network regulating TRIM63 expression.Methods and ResultsWe found that TFEB and transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) activate TRIM63 expression. The class IIa HDACs HDAC4, HDAC5, and HDAC7 inhibited this activity. Furthermore, we could map the HDAC5 and TFE3 physical interaction. PKD1, PKD2, and PKD3 reversed the inhibitory effect of all tested class IIa HDACs toward TFEB and TFE3. PKD1 mediated nuclear export of all HDACs and lifted TFEB and TFE3 repression. We also mapped the PKD2 and HDAC5 interaction. We found that the inhibitory effect of PKD1 and PKD2 toward HDAC4, HDAC5, and HDAC7 was mediated by their phosphorylation and 14-3-3 mediated nuclear export.ConclusionTFEB and TFE3 activate TRIM63 expression. Both transcription factors are controlled by HDAC4, HDAC5, HDAC7, and all PKD-family members. We propose that the multilevel PKD/HDAC/TFEB/TFE3 network tightly controls TRIM63 expression.

Published
2021
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2. 17β-Estradiol-induced interaction of ERα with NPPA regulates gene expression in cardiomyocytes

Author

Georgios Kararigas, Thi Hang Pham, Britta Fielitz, Vera Regitz-Zagrosek, Mercy M. Davidson, Arne Kuehne, George Petrov, Shokoufeh Mahmoodzadeh, and Elke Dworatzek

Subjects
Chromatin Immunoprecipitation, Transcription, Genetic, Physiology, Immunoprecipitation, Active Transport, Cell Nucleus, Fluorescent Antibody Technique, Biology, medicine.disease_cause, Transfection, Cell Line, Rats, Sprague-Dawley, Mice, Physiology (medical), Two-Hybrid System Techniques, Gene expression, Protein Interaction Mapping, medicine, Animals, Humans, Myocytes, Cardiac, Protein Interaction Domains and Motifs, RNA, Messenger, Protein Precursors, Receptor, Promoter Regions, Genetic, Mice, Knockout, Mutation, Estradiol, cDNA library, Estrogen Receptor alpha, Natriuretic Peptide, C-Type, Molecular biology, Chromatin, Cell biology, Rats, Cell nucleus, medicine.anatomical_structure, Animals, Newborn, Gene Expression Regulation, Mutagenesis, Site-Directed, Female, Cardiology and Cardiovascular Medicine, Chromatin immunoprecipitation, Atrial Natriuretic Factor, Protein Binding
Abstract

Aims 17β-Oestradiol (E2) and its receptors (ERα and ERβ) are important regulators of physiological and pathological processes in the cardiovascular system. ER act in concert with other regulatory factors mediating oestrogenic effects. However, the underlying mechanisms modulating ER transcriptional activity are not fully elucidated. To gain better understanding of E2-induced ERα action in the human heart, we aimed to identify and functionally analyse interaction partners of ERα. Methods and results Using yeast two-hybrid assays with a human heart cDNA library, we identified atrial natriuretic peptide precursor A (NPPA), a well-known cardiac hypertrophy marker, as a novel ERα interaction partner interacting in an E2-dependent manner. Mutation analyses and immunofluorescence data indicated that the LXXLL motif within NPPA is necessary for its E2-induced interaction with ERα, its action as a co-repressor of ERα, and its translocation into the nucleus of human and rat cardiomyocytes. Expression analysis and chromatin immunoprecipitation assays in a human left ventricular cardiomyocyte cell line, AC16, showed that NPPA interacts with E2/ERα, suppressing the transcriptional activity of ERα on E2-target genes, such as NPPA, connexin43, α actinin-2, nuclear factor of activated T-cells, and collagens I and III. Conclusion We characterize for the first time an E2-regulated interaction of NPPA with ERα in cardiomyocytes, that may be crucial in physiological and/or pathological cardiac processes, thereby representing a potential therapeutic target.

Published
2012

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