ArticleMolecular biology of the cell1998
Activation and cellular localization of the cyclosporine A-sensitive transcription factor NF-AT in skeletal muscle cells.
Article in Molecular biology of the cell, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 224 citations in OpenAlex.
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- Molecular Regulation of Porcine Skeletal Muscle Development: Insights from Research on CDC23 Expression and Function.International journal of molecular sciences · 2024Article
- Regulatory role of NFAT1 signaling in articular chondrocyte activities and osteoarthritis pathogenesis.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2023Article
- The circadian E3 ligase FBXL21 regulates myoblast differentiation and sarcomere architecture via MYOZ1 ubiquitination and NFAT signaling.PLoS genetics · 2022Article
- DYRK1A activates NFATC1 to increase glioblastoma migration.Cancer medicine · 2021Article
- Transcription factor signal transducer and activator of transcription 6 (STAT6) is an inhibitory factor for adult myogenesis.Skeletal muscle · 2021Article
- CaHeliyon · 2020Article
- Modeling the transport of nuclear proteins along single skeletal muscle cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers.Journal of cellular and molecular medicine · 2019Review
- Calcineurin Broadly Regulates the Initiation of Skeletal Muscle-Specific Gene Expression by Binding Target Promoters and Facilitating the Interaction of the SWI/SNF Chromatin Remodeling Enzyme.Molecular and cellular biology · 2019Article
- Non-equivalence of nuclear import among nuclei in multinucleated skeletal muscle cells.Journal of cell science · 2018Article
- Induction of Osmolyte Pathways in Skeletal Muscle Inflammation: Novel Biomarkers for Myositis.Frontiers in neurology · 2018Article
- Akirin2 regulates proliferation and differentiation of porcine skeletal muscle satellite cells via ERK1/2 and NFATc1 signaling pathways.Scientific reports · 2017Article
- Review
- Stromal interaction molecule 2 regulates C2C12 myoblast differentiation.Integrative medicine research · 2015Article
- Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme.Nature communications · 2015Article
- Effect of porcine Akirin2 on skeletal myosin heavy chain isoform expression.International journal of molecular sciences · 2015Article
- The Effect of SERCA1b Silencing on the Differentiation and Calcium Homeostasis of C2C12 Skeletal Muscle Cells.PloS one · 2015Article
- Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications.Tissue engineering. Part B, Reviews · 2014Review
- Calcineurin and glial signaling: neuroinflammation and beyond.Journal of neuroinflammation · 2014Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The widely used immunosuppressant cyclosporine A (CSA) blocks nuclear translocation of the transcription factor, NF-AT (nuclear factor of activated T cells), preventing its activity. mRNA for several NF-AT isoforms has been shown to exist in cells outside of the immune system, suggesting a possible mechanism for side effects associated with CSA treatment. In this study, we demonstrate that CSA inhibits biochemical and morphological differentiation of skeletal muscle cells while having a minimal effect on proliferation. Furthermore, in vivo treatment with CSA inhibits muscle regeneration after induced trauma in mice. These results suggest a role for NF-AT-mediated transcription outside of the immune system. In subsequent experiments, we examined the activation and cellular localization of NF-AT in skeletal muscle cells in vitro. Known pharmacological inducers of NF-AT in lymphoid cells also stimulate transcription from an NF-AT-responsive reporter gene in muscle cells. Three isoforms of NF-AT (NF-ATp, c, and 4/x/c3) are present in the cytoplasm of muscle cells at all stages of myogenesis tested. However, each isoform undergoes calcium-induced nuclear translocation from the cytoplasm at specific stages of muscle differentiation, suggesting specificity among NF-AT isoforms in gene regulation. Strikingly, one isoform (NF-ATc) can preferentially translocate to a subset of nuclei within a single multinucleated myotube. These results demonstrate that skeletal muscle cells express functionally active NF-AT proteins and that the nuclear translocation of individual NF-AT isoforms, which is essential for the ability to coordinate gene expression, is influenced markedly by the differentiation state of the muscle cell.
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