Studies on Protein Lipidation

描述(申请人提供)：蛋白质的动态S棕榈酰化控制着真核生物中各种尚未被很好理解的关键信号通路。我们实验室最近开发了强大的化学工具来快速分析蛋白质的动态S棕榈酰化，并大规模鉴定S棕榈酰化的蛋白质。拨款申请描述了我们的化学工具在分裂酵母中的应用，以剖析调节S棕榈酰化的机制。我们的初步研究发现，S棕榈酰化的缺陷会影响分裂酵母细胞的分裂(有丝分裂)或分化(减数分裂)。这些初步数据非常令人兴奋，因为它开始识别真核细胞用来控制决策和细胞命运的分子机制，并突出了Sz的作用。用于S机理研究的庞贝-棕榈酰化。因此，这项资助中提出的对动态S-棕榈酰化的详细分析对于了解细胞信号的基本机制是必不可少的，对于剖析与癌症和神经疾病等人类疾病相关的蛋白质S-棕榈酰化的缺陷也是重要的。 与公众健康相关：本提案描述了化学工具在裂解酵母中的开发和应用，以了解调节蛋白质S棕榈酰化的基本机制。这些研究将揭示S-棕榈酰化调控的新途径，这些途径尚未被很好地了解，并为与异常蛋白S-棕榈酰化相关的疾病提供重要的分子见解，如癌症和神经疾病。

DESCRIPTION (provided by applicant): Dynamic S-palmitoylation of proteins controls a variety of key signaling pathways in eukaryotes that are not well understood. Our laboratory has recently developed robust chemical tools to rapidly analyze dynamic S-palmitoylation of proteins and identify S-palmitoylated proteins on large-scale. The grant application describes that application of our chemical tools to fission yeast in order to dissect the mechanisms that regulated S-palmitoylation. Our preliminary studies have revealed defects in S-palmitoylation that influence whether fission yeast cells divide (mitosis) or differentiate (meiosis). These preliminary data are very exciting as it begins to identify molecular mechanisms that eukaryotic cells use to control decision-making and cell fate and highlights the utility of Sz. pombe for mechanistic studies in S-palmitoylation. The detailed analysis of dynamic S-palmitoylation proposed in this grant is therefore essential for understanding the basic mechanisms of cell signaling and is important for dissecting the defects in protein S-palmitoylation associated with human diseases such as cancer and neurological disorders. PUBLIC HEALTH RELEVANCE: This proposal describes the development and application of chemical tools to fission yeast to understand fundamental mechanisms that regulate protein S-palmitoylation. These studies should reveal new pathways modulated by S-palmitoylation that are not well understood and provide important molecular insight into diseases linked to aberrant protein S-palmitoylation such as cancer and neurological disorders.