Protein Palmitoylation in Yeast

酵母中的蛋白质棕榈酰化

• 批准号: 6623246
• 负责人: NICHOLAS G DAVIS
• 金额: $ 22.35万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623246
• 关键词: Animalia; Saccharomyces cerevisiae; biological signal transduction; cell free system; cell membrane; enzyme activity; enzyme complex; enzyme substrate; fatty acylation; fluorescence microscopy; fungal genetics; fungal proteins; gene mutation; immunofluorescence technique; intermolecular interaction; isozymes; mass spectrometry; molecular cloning; molecular site; palmitates; phosphotransferases; posttranslational modifications; protein localization; protein purification; protein structure function; vesicle /vacuole

DESCRIPTION (provided by applicant): Palmitoylation is one of several different lipid modifications that serve to target and anchor proteins to membranes in eukaryotic cells. Palmitoylation has been long-recognized for its role in directing the localization of a variety of signaling proteins, including key players in cancer like H- and K-Ras, Src, Lck, and Rho, to plasma membrane sites of action. Despite the long history, little has been learned regarding the enzymology of this modification - the responsible enzymatic activities have not been identified. Our recent work in the yeast Saccharornyces cerevisiae, indicates that the ankyrin-repeat protein Akr1p is required for palmitoylation and consequent membrane localization of the type I casein kinase, Yck2p; in akr1delta cells, Yck2p is not palmitoylated and as a consequence is mislocalized diffusely throughout the cytoplasm, rather than to the plasma membrane. The major goal of this proposal is to characterize the role of Akr1p in the palmitoylation process. Preliminary work indicates that Akr1p is a strong candidate to be an enzymatic component of the palmitoyl transferase. This will be tested. In addition, Akr1p-containing complexes will be purified from yeast to identify the proteins that collaborate with Akr1p for palmitoylation. Another significant fact regarding Akr1p is that is its closest human homolog is a protein identified for its possible role in Huntington's disease. Thus, these fundamental studies on the function of Akr1p in yeast may well impact our understanding of the disease processes in both cancer and in Huntington's disease.

描述（由申请人提供）：棕榈酰化是几种不同的 脂质修饰用于靶向和锚蛋白质到膜， 真核细胞棕榈酰化长期以来被认为是其在 指导各种信号蛋白的定位，包括关键的 癌症中的参与者，如H-和K-Ras，Src，Lck和Rho， 作用部位。尽管历史悠久，但人们对 这种修饰的酶学-负责的酶活性具有 未被确认。我们最近在酿酒酵母中的工作， 表明棕榈酰化需要锚定重复蛋白Akr1p 以及随后的I型酪蛋白激酶Yck2p的膜定位; 在akr1 δ细胞中，Yck2p未被棕榈酰化，因此， 错误定位弥漫在整个细胞质，而不是血浆 膜的该提案的主要目标是描述Akr1p的作用 在棕榈酰化过程中。初步研究表明，Akr1p是一种 强有力的候选者是棕榈酰转移酶的酶组分。 这将受到考验。此外，将纯化含Akr1p的复合物 从酵母中鉴定出与Akr1p合作的蛋白质， 棕榈酰化关于Akr1p的另一个重要事实是， 人类同源物是一种蛋白质，其被鉴定为在亨廷顿舞蹈症中可能起作用， 疾病因此，这些关于Akr1p在酵母中的功能的基础研究可能会 很好地影响了我们对癌症和癌症中疾病过程的理解， 亨廷顿氏病。