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Processing and activation of CMH-1 by granzyme B
Y Gu1, C Sarnecki, M A Fleming
1Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139, USA.
The Journal of Biological Chemistry
|May 3, 1996
Summary
Granzyme B (GB) cleaves and activates CMH-1, a protease similar to CPP32. This suggests CMH-1 may also contribute to cytotoxic T lymphocyte (CTL)-mediated cell killing.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Granzyme B is crucial for cytotoxic T lymphocyte (CTL) mediated killing.
- Granzyme B is suspected to activate CPP32, a cysteine protease, to mediate its cytotoxic effects.
- CMH-1 is a homologue of CPP32.
Purpose of the Study:
- To investigate the in vitro processing and activation of CMH-1 by Granzyme B.
- To determine the specific cleavage sites and their role in CMH-1 activation.
Main Methods:
- In vitro cleavage assays using purified Granzyme B and CMH-1.
- Analysis of cleavage products to identify specific cleavage sites.
Main Results:
- Granzyme B specifically cleaves CMH-1 at Asp198-Ser199, activating the protease.
- Autocatalytic cleavage at Asp23-Ala24 is not essential for CMH-1 activity.
- This cleavage by Granzyme B activates CMH-1.
Conclusions:
- Granzyme B directly cleaves and activates CMH-1 in vitro.
- CMH-1, like CPP32, may play a role in cytotoxic T lymphocyte (CTL)-mediated cell killing.
- These findings elucidate a novel mechanism in immune cell cytotoxicity.