Involvement of Histone H1.2 in Apoptosis Induced by DNA Double-Strand Breaks
Autor: | Yoshihide Tsujimoto, Yoshitaka Fujii, Yosuke Matsuoka, Junko Hirota, Akimitsu Konishi, Shigeomi Shimizu, Toshifumi Takao, Yoshihiro Yoneda, Arthur I. Skoultchi, Lilin Zhang, Yuhong Fan |
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Rok vydání: | 2003 |
Předmět: |
Male
Ultraviolet Rays DNA damage Apoptosis Cytochrome c Group Thymus Gland Biology Mitochondrion General Biochemistry Genetics and Molecular Biology Histones Mice Histone H1 Intestine Small Animals Humans Protein Isoforms APAF1 Phosphoenolpyruvate Sugar Phosphotransferase System Etoposide Cell Nucleus Mice Knockout Tumor Necrosis Factor-alpha Biochemistry Genetics and Molecular Biology(all) Escherichia coli Proteins X-Rays Cytochrome c Membrane Proteins Proteins Molecular biology Mitochondria Rats Apoptotic Protease-Activating Factor 1 Eukaryotic Cells bcl-2 Homologous Antagonist-Killer Protein Histone Cytoplasm biology.protein Tumor Suppressor Protein p53 DNA Damage |
Zdroj: | Cell. 114(6):673-688 |
ISSN: | 0092-8674 |
DOI: | 10.1016/s0092-8674(03)00719-0 |
Popis: | It is poorly understood how apoptotic signals arising from DNA damage are transmitted to mitochondria, which release apoptogenic factors into the cytoplasm that activate downstream destruction programs. Here, we identify histone H1.2 as a cytochrome c-releasing factor that appears in the cytoplasm after exposure to X-ray irradiation. While all nuclear histone H1 forms are released into the cytoplasm in a p53-dependent manner after irradiation, only H1.2, but not other H1 forms, induced cytochrome c release from isolated mitochondria in a Bak-dependent manner. Reducing H1.2 expression enhanced cellular resistance to apoptosis induced by X-ray irradiation or etoposide, but not that induced by other stimuli including TNF-α and UV irradiation. H1.2-deficient mice exhibited increased cellular resistance in thymocytes and the small intestine to X-ray-induced apoptosis. These results indicate that histone H1.2 plays an important role in transmitting apoptotic signals from the nucleus to the mitochondria following DNA double-strand breaks. |
Databáze: | OpenAIRE |
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