Small heat shock protein gene expression and function in xenopus

非洲爪蟾小热休克蛋白基因表达和功能

• 批准号: 2820-2009
• 负责人: Heikkila, John
• 金额: $ 3.64万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=520516
• 关键词: Small; heat; shock; protein; gene

Healthy cells require the synthesis and maintenance of correctly folded proteins. Environmental stresses and disease states can perturb this situation and if left unchecked could result in cell death. Small heat shock proteins (sHsps) are a class of molecular chaperones that play important roles in cellular homeostasis and protein folding as well as protecting the cell against numerous stresses including heat shock and exposure to heavy metals, reactive oxygen species and arsenite. During cellular stress, sHsps, in their role as molecular chaperones, bind to denatured protein, inhibit their aggregation, and facilitate their refolding once favorable conditions have returned. Also, sHsp synthesis or mutations have been associated with various diseases such as cancer, multiple sclerosis, various neuropathologies and muscle myopathy. Over the past 23 years, the applicant's laboratory has been actively researching sHsp gene expression and function in the model frog system, Xenopus laevis. They have made significant progress in the characterization of expression and function of the sHsp family, Hsp30. Recently, they reported on the presence and molecular chaperone function of a second Xenopus sHsp, Hsp27, a human Hsp27 homolog. The long term goals of the applicant's research program are to understand the regulation and function of Xenopus sHsps. The specific aims of this grant proposal are to: 1) analyze the mechanism(s) associated with developmental regulation of Hsp30 gene expression, 2) characterize the molecular chaperone domains of Hsp30 and Hsp27, 3) determine the effect of Hsp30 and Hsp27 depletion in heat shocked Xenopus embryos, 4) examine the effect of proteasomal inhibition on sHsp gene expression in cultured cells and embryos, and 5) characterize the effect of cadmium on Hsp30 and Hsp27 gene expression in Xenopus cultured cells and embryos. This hypothesis-driven research proposal will build on previous work and explore new areas related to sHsp gene expression and function. Knowledge regarding sHsp structure and function will provide a better understanding of various disease states.

健康的细胞需要合成和维持正确折叠的蛋白质。环境压力和疾病状态会扰乱这种情况，如果不加以控制，可能导致细胞死亡。小分子热休克蛋白（Small heat shock proteins，sHsps）是一类分子伴侣蛋白，在维持细胞内环境稳定、蛋白质折叠以及保护细胞免受热休克、重金属、活性氧和砷等多种应激中发挥重要作用。在细胞应激期间，sHsps作为分子伴侣与变性蛋白结合，抑制其聚集，并在有利条件恢复后促进其重折叠。此外，sHsp合成或突变与各种疾病如癌症、多发性硬化症、各种神经病理学和肌肉肌病相关。在过去的23年里，申请人的实验室一直在积极研究sHsp基因在模式蛙系统非洲爪蟾中的表达和功能。他们在sHsp家族Hsp30的表达和功能的表征方面取得了重大进展。最近，他们报道了第二种非洲爪蟾sHsp，Hsp27，一种人类Hsp27同源物的存在和分子伴侣功能。申请人研究计划的长期目标是了解非洲爪蟾sHsps的调节和功能。这项赠款建议的具体目标是：1）分析与Hsp30基因表达的发育调节相关的机制，2）表征Hsp30和Hsp27的分子伴侣结构域，3）确定热休克爪蟾胚胎中Hsp30和Hsp27缺失的效果，4）检测蛋白酶体抑制对培养细胞和胚胎中sHsp基因表达的效果，和5）表征镉对非洲爪蟾培养细胞和胚胎中Hsp30和Hsp27基因表达的影响。这一假设驱动的研究提案将建立在以前的工作基础上，并探索与sHsp基因表达和功能相关的新领域。关于sHsp结构和功能的知识将提供对各种疾病状态的更好理解。