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Proteasome and Ubiquitin System

Unraveling the multitude of biological phenomena regulated by protein degradation
Keywords: Intracellular protein degradation, proteasome, ubiquitin, cancer, aging, immunity

Research Topics

  1. Determination of the operation mechanism of the proteasome, a macromolecular protein degradation enzyme, and unraveling the relationship between proteasome functional abnormalities and disease (cancer, inflammation, aging, neurodegeneration)
  2. Elucidation of the selection mechanism of T cells by thymus-specific proteasomes
  3. Unraveling protein quality control mechanisms by the ubiquitin system

At the laboratory of protein metabolism, our main topic is unraveling mechanisms of cell function regulation by the cellular protein degradation machine, the proteasome. We perform research using a wide range of methods such as cell biology, biochemistry, mouse developmental engineering, and yeast and fly genetics.

The proteasome regulates a diverse range of functions necessary for life such as regulation of the cell cycle, transcription, signal transduction, and protein quality control, through degradation of ubiquitinated proteins. In recent years, it has become apparent that an increase or decrease in the amount or activity of proteasomes is related to numerous human diseases or physiological effects such as cancer, neurodegeneration, metabolic disorders, stem cell maintenance, and aging. However the precise molecular mechanisms of how proteasome expression levels or activities are regulated, and how changes in proteasome function levels are related to diseases and physiological phenomena remains unknown. The goal of our lab is to unravel mechanisms regulating the proteasome, and understand how proteasome dysfunction leads to the above diseases.