The interaction between tRNA and cytochrome c in apoptosis of cancer cells

tRNA与细胞色素c的相互作用在癌细胞凋亡中的作用

基本信息

批准号：
8692304
负责人：
Xiaolu Yang
金额：
$ 17.4万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-05 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8692304
关键词：
ATP Synthesis Pathway Adaptor Signaling Protein Address Amino Acids Animal Model Anticodon Apoptosis Apoptosis Regulator Apoptotic Binding Biology Cancer cell line Caspase Cell Death Cell Death Process Cells Cessation of life Clinical Trials Combined Modality Therapy Cues Cytoplasm DNA Damage Electron Transport Eukaryota Event Exhibits Gene Expression Genetic Code Genetic Translation Grant Homeostasis Hydrolysis Immunity In Vitro Individual Life Ligands Malignant Neoplasms Malignant neoplasm of lung Mitochondria Modality Modeling Normal Cell Oncogene Activation Onconase Oxidative Phosphorylation Pathway interactions Peptide Hydrolases Pharmaceutical Preparations Physiological Processes Play Proteins RNA Radiation therapy Regulation Resistance Ribonucleases Role Testing Toxic effect Transfer RNA Vertebrates apoptotic protease-activating factor 1 base cancer cell cancer therapy caspase-9 cellular development cytochrome c follow-up human CASP4 protein improved in vivo killings mutant neoplastic cell new therapeutic target preference prevent public health relevance research study tumor tumor progression tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): This project seeks to characterize how the interaction between transfer RNA (tRNA) and cytochrome c (cyt c) modulates apoptosis of cancer cells. tRNA and cyt c are ancient molecules with fundamental roles in biology. In healthy cells the major function of tRNA and cyt c are to interpret the genetic code by connecting amino acids to anticodons and to transport electrons in oxidative phosphorylation, respectively. Cyt c is also a defining player in the intrinsic apoptosis pathway, which is critical for protection from cancer. W recently found that tRNA inhibits the pro-apoptotic activity of cyt c by preventing the interaction of cyt c with the caspase activator Apaf-1. We will investigate the functional interaction between tRNA and cyt c in cancer cell death and to explore the utility of this interaction as a novel therapeutic target. Our central hypothesis is that high levels of tRNA in tumor cells contribute to apoptosis resistance and tumorigenesis, and targeting tRNA is beneficial in tumor therapy. We propose three specific aims: 1) Define the role of tRNA in the intrinsic apoptosis pathway; 2) Investigate the sensitivity of cancer cells to tRNA hydrolysis; and 3) Determine the combined effect of the tRNA-specific RNase Onconase and agents that invoke the intrinsic apoptosis pathway in tumor therapy. The experiments outlined here will improve our understanding of tRNA in the fundamental processes of cell death, and will inform therapies in cancer.

描述（由申请人提供）：该项目旨在描述转移 RNA (tRNA) 和细胞色素 c (cyt c) 之间的相互作用如何调节癌细胞的凋亡。 tRNA 和 cyt c 是在生物学中具有重要作用的古老分子。在健康细胞中，tRNA 和 cyt c 的主要功能分别是通过将氨基酸与反密码子连接来解释遗传密码，并在氧化磷酸化中传输电子。 Cyt c 也是内在细胞凋亡途径的决定性参与者，这对于预防癌症至关重要。 W 最近发现 tRNA 通过阻止相互作用来抑制细胞色素 c 的促凋亡活性细胞色素 c 与 caspase 激活剂 Apaf-1。我们将研究 tRNA 和 cyt c 在癌细胞死亡中的功能相互作用，并探索这种相互作用作为新治疗靶点的效用。我们的中心假设是肿瘤细胞中高水平的 tRNA 有助于细胞凋亡抵抗和肿瘤发生，靶向tRNA有利于肿瘤治疗。我们提出了三个具体目标：1）定义 tRNA 在内在凋亡途径中的作用； 2）研究癌细胞对tRNA水解的敏感性； 3) 确定 tRNA 特异性 RNase Onconase 和在肿瘤治疗中调用内在细胞凋亡途径的药物的联合作用。这里概述的实验将提高我们对细胞死亡基本过程中 tRNA 的理解，并为癌症治疗提供信息。