Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a specific substrate of yeast metacaspase

Biochim Biophys Acta. 2011 Dec;1813(12):2044-9. doi: 10.1016/j.bbamcr.2011.09.010. Epub 2011 Oct 1.


Yeast metacaspase (Yca1p) is required for the execution of apoptosis upon a wide range of stimuli. However, the specific degradome of this yeast protease has not been unraveled so far. By combining different methodologies described as requisites for a protein to be considered a protease substrate, such as digestome analysis, cleavage of recombinant GAPDH by metacaspase and evaluation of protein levels in vivo, we show that upon H(2)O(2)-induced apoptosis, the metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a specific target of metacaspase. Nitric oxide (NO) signaling, which mediates H(2)O(2)-induced apoptosis, is required for metacaspase specific GAPDH cleavage. In conclusion, in this work we identified GAPDH as the first direct yeast metacaspase substrate described so far. Although mammalian caspases and yeast metacaspase apparently have distinct target cleavage sites, GAPDH arises as a common substrate for these proteases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis / drug effects*
  • Caspases / metabolism*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism*
  • Hydrogen Peroxide / pharmacology*
  • Immunoblotting
  • Molecular Sequence Data
  • Nitric Oxide / metabolism*
  • Oxidants / pharmacology
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Sequence Homology, Amino Acid


  • Oxidants
  • Reactive Oxygen Species
  • Recombinant Proteins
  • Nitric Oxide
  • Hydrogen Peroxide
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Caspases