Studies on Protein Lipidation

描述（由申请人提供）：蛋白质的动态S-棕榈酰化控制着真核生物中尚未充分了解的多种关键信号通路。我们的实验室最近开发了强大的化学工具，可以快速分析蛋白质的动态S-棕榈酰化，并大规模鉴定S-棕榈酰化蛋白质。资助申请描述了我们的化学工具在裂变酵母中的应用，以剖析调节S-棕榈酰化的机制。我们的初步研究揭示了S-棕榈酰化的缺陷，影响是否分裂酵母细胞分裂（有丝分裂）或分化（减数分裂）。这些初步数据非常令人兴奋，因为它开始确定真核细胞用于控制决策和细胞命运的分子机制，并突出了Sz的实用性。粟酒裂殖酵母用于S-棕榈酰化的机理研究。因此，本研究中提出的动态S-棕榈酰化的详细分析对于理解细胞信号传导的基本机制至关重要，并且对于解剖与人类疾病（如癌症和神经系统疾病）相关的蛋白质S-棕榈酰化缺陷非常重要。 公共卫生相关性：该提案描述了裂变酵母的化学工具的开发和应用，以了解调节蛋白质S-棕榈酰化的基本机制。这些研究应该揭示S-棕榈酰化调节的新途径，这些途径尚未得到很好的理解，并为与异常蛋白S-棕榈酰化相关的疾病（如癌症和神经系统疾病）提供重要的分子见解。

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.