C3G shows regulated nucleocytoplasmic exchange and represses histone modifications associated with euchromatin
| Autor: | Kunal Dayma, Vegesna Radha, C. Varalakshmi, Anesh Ramadhas, Dhruv Kumar Shakyawar |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Euchromatin Cellular differentiation Nuclear Localization Signals Active Transport Cell Nucleus Biology Muscle Development environment and public health 03 medical and health sciences Glycogen Synthase Kinase 3 Mice Cell Line Tumor Histone code Animals Guanine Nucleotide Exchange Factors Phosphorylation Nuclear export signal Molecular Biology Guanine Nucleotide-Releasing Factor 2 Cell Proliferation Cell Nucleus Nuclear Functions Cell Differentiation Cell Biology Articles Nuclear matrix Actins Chromatin Cell biology Up-Regulation Histone Code 030104 developmental biology Histone biology.protein Fatty Acids Unsaturated Nuclear localization sequence Signal Transduction |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | C3G (RapGEF1), essential for mammalian embryonic development, shows dynamic nucleocytoplasmic exchange. Nuclear localization is regulated by NLSs, NES, and phosphorylation. C3G translocates to the nucleus in response to physiological stimuli and regulates chromatin modifications and gene expression. C3G (RapGEF1) is a ubiquitously expressed guanine nucleotide exchange factor that functions in signaling pathways regulating cell proliferation, apoptosis, and actin reorganization. It is essential for differentiation and early embryonic development in mice. Overexpressed C3G shows predominant cytoplasmic localization, but endogenous C3G is a component of nuclear fractions in a variety of cell types. Coexpression of importin-α and inhibition of nuclear export by leptomycin B resulted in predominant nuclear localization of C3G. Functional NLSs, NES, and GSK3-β–dependent phosphorylation regulate its dynamic nuclear localization. C3G translocates to the nucleus in response to myogenic differentiation and sublethal dose of cisplatin. C3G is associated with chromatin and nuclear matrix fractions. Cells with C3G localized in the nucleus showed peripheralization of heterochromatin and reduced histone modifications associated with euchromatin. Short hairpin RNA–mediated depletion of C3G in epithelial cells resulted in reduced expression of CDK inhibitors and the histone demethylase KDM5A. Myoblast clones with CRISPR/Cas9-mediated knockout of C3G failed to show repression of histone marks and did not show up-regulation of myosin heavy chain and myotube formation when grown in differentiation medium. Our results document regulated nucleocytoplasmic exchange of C3G in response to physiological stimuli and provide insights into nuclear functions for C3G. |
| Databáze: | OpenAIRE |
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