Wang, X., Merritt, A.J., Seyfried, J. et al. (9 more authors) (2005) Targeted deletion of mek5 causes early embryonic death and defects in the extracellular signal-regulated kinase 5/myocyte enhancer factor 2 cell survival pathway. Molecular and Cellular Biology, 25 (1). pp. 336-345. ISSN 0270-7306
Abstract
To elucidate the physiological significance of MEK5 in vivo, we have examined the effect of mek5 gene elimination in mice. Heterozygous mice appear to be healthy and were fertile. However, mek5-/- embryos die at approximately embryonic day 10.5 (E10.5). The phenotype of the mek5 -/- embryos includes abnormal cardiac development as well as a marked decrease in proliferation and an increase in apoptosis in the heart, head, and dorsal regions of the mutant embryos. The absence of MEK5 does not affect cell cycle progression but sensitizes mouse embryonic fibroblasts (MEFs) to the ability of sorbitol to enhance caspase 3 activity. Further studies with mek5-/- MEFs indicate that MEK5 is required for mediating extracellular signal-regulated kinase 5 (ERK5) activation and for the regulation of the transcriptional activity of myocyte enhancer factor 2. Overall, this is the first study to rigorously establish the role of MEK5 in vivo as an activator of ERK5 and as an essential regulator of cell survival that is required for normal embryonic development.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2005, American Society for Microbiology. |
Keywords: | Animals; Apoptosis; Blotting, Southern; Caspase 3; Caspases; Cell Death; Cell Proliferation; Cell Survival; Cells, Cultured; DNA-Binding Proteins; Enzyme Activation; Fibroblasts; Flow Cytometry; Gene Deletion; Genes, Reporter; Genetic Vectors; Genotype; Heterozygote; Immunoblotting; Immunohistochemistry; In Situ Nick-End Labeling; Luciferases; MAP Kinase Kinase 5; MEF2 Transcription Factors; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 7; Models, Genetic; Mutation; Myocardium; Myogenic Regulatory Factors; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Time Factors; Tissue Distribution; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transgenes |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 26 Jul 2023 10:20 |
Last Modified: | 26 Jul 2023 10:26 |
Status: | Published |
Publisher: | Informa UK Limited |
Refereed: | Yes |
Identification Number: | 10.1128/mcb.25.1.336-345.2005 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:201806 |