第３２回生命医科学セミナー（Biomedical Science Seminar）
演 題：The role of DDB2 (XP-E) in Tumor Suppression and Apoptosis
演 者：Dr. Stuart Linn
Dept of Molec. and Cell Biol., The University of California
日 時：平成２５年９月１７日（火） １８：００～１９：００
場 所：病院地区総合研究棟１階 １０５セミナー室
DDB is a heterodimer of p48/DDB2, which is found only in higher eukaryotes, and p127/DDB1, that is ubiquitous among eukaryotes. Mutations in human DDB2 generate xeroderma pigmentosum Group E and fibroblasts from XP-E individuals are resistant to killing by UV due to a deficiency in UV-induced apoptosis, reflecting reduced basal- and UV-induced p53 levels. Ddb2-/- mice have enhanced skin tumors and cataract formation after UV irradiation, but do not respond abnormally to γ-ray or DMBA exposure. Both Ddb2-/- and Ddb2+/- mice have shortened life spans and an enhanced frequency and spectrum of spontaneous tumors, particularly lung and mammary adenocarcinomas. Ddb2-/- mice are smaller than normal and, whereas the sizes of kidneys and livers are reduced proportionately, spleens gradually enlarge with age due to lymphoid proliferation. Ddb2-/- mice have larger testes due to decreased testicular germ cell spontaneous apoptosis, reflecting reduced levels of p53 in the cells. Tumors that appear in heterozygous Ddb2+/- mice conserve the wild type Ddb2 allele, Ddb2 RNA expression, and Ddb2 exon sequences. Therefore, Ddb2 heterozygosity can facilitate tumor development as a haploinsufficient tumor suppressor. A scheme will be proposed for DDB action after UV irradiation that involves the Cullin4-DDB1-DDB2 ubiquitin ligase and the degradation of KAT3B (CBP/p300) acting as a DNA damage dosimeter for the signal to initiate apoptosis.
共 催：福岡医学会
問合せ：九州大学大学院 医学研究院 基礎放射線医学分野 續 輝久（内線６１４１）
