CK1delta/epsilon Inhibits Apoptosis in Drosophila

CK1delta/epsilon 抑制果蝇细胞凋亡

• 批准号: 7050184
• 负责人: Jennifer Kennell
• 金额: $ 4.6万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7050184
• 关键词: Drosophilidae; JUN kinase; apoptosis; arthropod genetics; casein kinase; cysteine endopeptidases; enzyme activity; gene expression; genetic screening; guanine nucleotide binding protein; imaginal disc; phosphorylation; postdoctoral investigator; protein degradation; protein protein interaction; protein structure function; tissue /cell culture; ubiquitin

DESCRIPTION (provided by applicant): Apoptosis, or programmed cell death, is critical for development and maintenance of tissue homeostasis. Important negative regulators of caspase activity are a family of proteins called inhibitors of apoptosis (IAP). A well characterized Drosophila IAP, DIAP1, is critical for inhibition of apoptosis. DIAP1 is regulated by a group of proteins, called IAP regulatory proteins that bind to and inhibit its activity. Well-characterized Drosophila members of the IAP regulatory proteins include Reaper, Hid and Grim. The Cadigan lab has carried out a genetic screen and identified discs overgrown (dco), a Drosophila homologue of casein kinase-delta/epsilon, as an inhibitor of hid-dependent apoptosis when overexpressed. Consistent with its overexpression phenotype, loss of dco in the wing imaginal disc resulted in elevated levels of apoptosis and decreased levels of DIAP1 protein. We hypothesize that Dco either inhibits Hid and/or activates DIAP1 to inhibit apoptosis. I will utilize cell culture and in vitro biochemical analysis to determine whether Dco interacts directly with Hid or DIAP1. In addition, I will use genetic approaches to identify additional genes that are involved in dco-dependent inhibition of apoptosis.

描述（由申请人提供）：细胞凋亡，或程序性细胞死亡，对组织稳态的发展和维持至关重要。caspase活性的重要负调节因子是称为凋亡抑制剂（IAP）的蛋白质家族。果蝇的IAP， DIAP1，在抑制细胞凋亡中起关键作用。DIAP1受一组称为IAP调节蛋白的蛋白质调节，这些蛋白质结合并抑制其活性。已知的果蝇IAP调节蛋白成员包括Reaper、Hid和Grim。Cadigan实验室进行了一项基因筛选，发现了过度生长的盘状细胞（dco），这是酪蛋白激酶- δ /epsilon的果蝇同源物，当过度表达时，它可以抑制隐藏依赖性细胞凋亡。与其过表达表型一致的是，dco在翅膀成像盘的缺失导致细胞凋亡水平升高和DIAP1蛋白水平降低。我们假设Dco通过抑制Hid和/或激活DIAP1来抑制细胞凋亡。我将利用细胞培养和体外生化分析来确定Dco是否直接与Hid或DIAP1相互作用。此外，我将使用遗传方法来确定参与dco依赖性细胞凋亡抑制的其他基因。