MARC Predoctoral Fellowship Program

MARC 博士前奖学金计划

• 批准号: 7354065
• 负责人: Rebecca Baerga
• 金额: $ 2.34万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2008-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7354065
• 关键词: Address; Animal Model; Autophagocytosis; Breast; CCL7 gene; Cell Line; Class; Complex; Data; Embryo; Fellowship Program; Genes; Genetic; Growth; Human; Immunoprecipitation; Knockout Mice; MCF7 cell; Malignant Neoplasms; Malignant neoplasm of prostate; Mass Spectrum Analysis; Molecular; Molecular Weight; Mono-S; Monoclonal Antibodies; Mus; Numbers; Ovarian; Phosphorylation; Phosphorylation Site; Phosphotransferases; Play; Post-Translational Modification Site; Post-Translational Protein Processing; Process; Proteins; Regulation; Role; Site-Directed Mutagenesis; Starvation; System; Therapeutic; Tumor Suppression; Tumor Suppressor Genes; Western Blotting; Work; Yeasts; base; cancer therapy; insight; mutant; novel; pre-doctoral; prevent; programs; protein degradation; tool; tumor; tumorigenesis

The process of autophagy is a complex catabolic program for lysosomal degradation of proteins and other subcellular constituents. It is important for normal growth control and is defective in a number of cancers. Beclin 1 gene is the first mammalian gene identified involved in autophagy. Mono-allelic deletions of Beclin 1 gene are identified in 40 -75% of human sporadic breast, ovarian and prostate cancers. Homozygous Beclin 1 knockout mice are embryonic lethal, while the heterozygous Beclin 1 knockout mice develop various tumors. This mouse genetic result provides compelling evidence that autophagy plays an important role in preventing tumorigenesis. However, exactly why the Beclin 1 gene and autophagy are critical for tumor suppression remains unknow. The re-activation of autophagy may be an efficient cancer therapeutic strategy. Preliminary data indicates that exogenous expression of the Beclin 1 mutant which mimics constitutive phosphorylation in MCF7 cells results in the activation of autophagy. This tool will be used to consfruct cellular and animal models to characterize the consequence of re-activating autopahgy.

自噬的过程是一个复杂的分解代谢程序，用于蛋白质和其他蛋白质的溶酶体降解。 亚细胞成分它对正常生长控制很重要，在许多癌症中是有缺陷的。 Beclin 1基因是第一个被发现参与自噬的哺乳动物基因。Beclin 1的单等位基因缺失 在40 - 75%的人散发性乳腺癌、卵巢癌和前列腺癌中鉴定出了该基因。纯合子Beclin Beclin 1基因敲除小鼠是胚胎致死的，而杂合Beclin 1基因敲除小鼠发育成各种不同的细胞。 肿瘤的这一小鼠遗传结果提供了令人信服的证据，表明自噬在 防止肿瘤发生。然而，为什么Beclin 1基因和自噬对肿瘤至关重要， 镇压仍是未知数。自噬的重新激活可能是一种有效的癌症治疗方法 战略初步数据表明，Beclin 1突变体的外源表达， MCF 7细胞中的组成性磷酸化导致自噬的激活。该工具将用于 构建细胞和动物模型来表征重新激活自噬的后果。