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TARGETS OF A MECHANISM-BASED PROBE AGAINST CYSTEINE PROTEASES

TARGETS OF A MECHANISM-BASED PROBE AGAINST CYSTEINE PROTEASES
基于机制的半胱氨酸蛋白酶探针的靶标
批准号:
8169165
负责人:
Tom Muir
金额:
$0.12万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-03-01 至 2011-02-28

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中文摘要
翻译
这个子项目是众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Using LC-MS/MS, we have identified the target of a mechanism-based probe against cysteine proteases upregulated during apopotosis as Cathepsin B, implicating its activity in cell death. Cells control their own death through a program termed apoptosis, which is indispensable for development and homeostasis in all metazoans. Lysosomal cysteine proteases are not normally thought of as participating in apoptosis; however, recent reports have shown that the cathepsin proteases can be released from the lysosome during apoptosis, where they can participate in cell death. We report here the development of an activity-based probe that, under optimized conditions, reports on cathepsin B activity only in apoptotic cells by reading out the release of cathepsin B from the lysosomes. Biochemical characterization of apoptosis in cells from cathepsin B null mice shows delayed and suboptimal activation of caspases. Our data further supports a role for cathepsin B in the cytosol as a positive regulator of a cell death feed-forward loop and provides a chemical tool for future investigations. This work has been published in Chem. Biol.
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Project 3: Mechanisms of Methyltransferase Dysregulation by Oncohistones
  • 批准号:
    10024845
  • 项目类别:
  • 资助金额:
    $27.1万
  • 财政年份:
    2015
  • 负责人:
    Tom Muir
  • 依托单位:
Project 3: Mechanisms of Methyltransferase Dysregulation by Oncohistones
  • 批准号:
    10269906
  • 项目类别:
  • 资助金额:
    $21.13万
  • 财政年份:
    2015
  • 负责人:
    Tom Muir
  • 依托单位:
Development and Applications of 'Designer Chromatin'
  • 批准号:
    9060364
  • 项目类别:
  • 资助金额:
    $30.17万
  • 财政年份:
    2013
  • 负责人:
    Tom Muir
  • 依托单位:
Development and Applications of 'Designer Chromatin'
  • 批准号:
    8556589
  • 项目类别:
  • 资助金额:
    $29.77万
  • 财政年份:
    2013
  • 负责人:
    Tom Muir
  • 依托单位:
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