Author/Authors :
Akimitsu Konishi، نويسنده , , Shigeomi Shimizu، نويسنده , , Junko Hirota، نويسنده , , Toshifumi Takao، نويسنده , , Yuhong Fan، نويسنده , , Yosuke Matsuoka، نويسنده , , Lilin Zhang، نويسنده , , Yoshihiro Yoneda، نويسنده , , Yoshitaka Fujii، نويسنده , , Arthur I. Skoultchi، نويسنده , , Yoshihide Tsujimoto، نويسنده ,
Abstract :
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.
