朊病毒揭示了复杂的特征和表型多样性-猫眼课题宝

朊病毒揭示了复杂的特征和表型多样性

批准号：

8645641

负责人：

HEATHER L TRUE-KROB

金额：

$35.72万

依托单位：

WASHINGTON UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2005

资助国家：

美国

项目状态：

已结题

起止时间：

2005-08-01 至 2017-04-30

来源：

https://reporter.nih.gov/project-details/8645641

关键词：

Adopted Alzheimer&apos s Disease Amyloid Area Attention Biology Cell Cycle Progression Cell Death Cell physiology Cells Complex Cytoplasm Data Development Disease Elements Employee Strikes Environment Epigenetic Process Event Evolution Fiber Funding Gene Expression Regulation Genetic Goals Huntington Disease Inherited Investigation Lead Life Malignant Neoplasms Mediating Metabolic Molecular Conformation Mothers Nature Neurodegenerative Disorders Nutrient Organism Parkinson Disease Phenotype Post-Translational Protein Processing PrP Prion Diseases Prions Process Protein Structure Initiative Proteins Regulation Reporter Research Saccharomyces cerevisiae Saccharomycetales Signal Transduction Stress Structure System Translations Variant Virus Work Yeasts base cell growth daughter cell environmental change gain of function human disease interest loss of function non-genetic non-prion novel overexpression pathogen polymerization premature prion hypothesis protein aggregate protein expression protein function protein misfolding protein structure protein structure function response sup35 termination factor trait transmission process yeast prion

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DESCRIPTION (provided by applicant): Proteins must adopt the correct folded structure for full functionality. For some proteins, post-translational modifications have a tremendous impact on both the structure and the function of the protein. Structural regulatory control of protein function has been well- established in many facets of biology and is often a key control step in signal transduction events that are essential for life, such as the response to nutrients and stresses, cell cycle progression, and proliferation. However, unexpected alterations in protein structure can be detrimental. Misfolded proteins are frequently associated with irreversible loss-of-function and disease instead of regulation. Protein misfolding and aberrant polymerization have been implicated in many neurodegenerative disorders including Parkinson's, Alzheimer's, Huntington's, and prion diseases. We are investigating how a group of proteins adopt a specific type of "misfolded" state (prion conformation) as a regulatory mechanism. These proteins may have evolved with the intrinsic ability to produce major changes in conformation as a means of regulation. This mechanism (prion propagation) provides an epigenetic switch that is self-perpetuating and is transmitted from mother cells to their daughter cells when the prion protein is transmitted through the cytoplasm. Due to their unique mode of propagation and inheritance, these prions have a profound impact on the ability of the organism to alter its phenotypes and adapt to changing environments. These prion proteins may represent remnants of an ancient regulatory mechanism that is still maintained in the budding yeast Saccharomyces cerevisiae. We now have evidence to suggest that phenotypic adaptation can be regulated by a network of prion proteins in yeast. Elucidating the underlying mechanistic principles of this epigenetic mechanism of regulation is a key first step in revealing the global impact of this type of regulation on protein expression to alter phenotypes, adaptation, and survival.

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