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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
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Blessing or curse? Proteomics in granzyme research.

Lars T Joeckel1, Phillip I Bird

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Granzymes (gzms) are serine proteases involved in immunity and disease. Proteomic studies identify many new substrates, but physiological relevance remains unclear, necessitating further investigation.

Keywords:
GranzymeSerine proteasesSubstrate specificity

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Area of Science:

  • Immunology
  • Proteomics
  • Molecular Biology

Background:

  • Granzymes (gzms) are serine proteases crucial for immunity, inflammation, and various diseases like cancer and sepsis.
  • While traditionally known for cytotoxic lymphocyte-mediated cell death, gzms also exhibit extracellular functions.
  • Five human granzymes (A, B, H, K, M) possess distinct substrate specificities.

Purpose of the Study:

  • To review and analyze proteomic approaches for mapping granzyme cleavage specificity and identifying substrates.
  • To discuss the convincing and controversial outcomes of these proteomic studies.
  • To clarify the physiological relevance of identified granzyme substrates.

Main Methods:

  • Proteomic techniques to map granzyme cleavage sites and identify substrates.
  • Analysis of existing literature on granzyme function and substrate identification.
  • Cross-referencing identified substrates with independent experimental validation.

Main Results:

  • Proteomic studies have significantly expanded the known substrate repertoire for human granzymes.
  • Numerous new substrates have been uncovered, refining understanding of granzyme specificity.
  • The physiological relevance of most identified substrates, except for a few granzyme B targets, remains largely unconfirmed.

Conclusions:

  • Proteomic approaches are powerful tools for exploring granzyme biology.
  • Further validation is critical to establish the physiological significance of newly identified granzyme substrates.
  • Understanding granzyme functions is essential for developing therapeutic strategies against related diseases.