ER stress does not cause upregulation and activation of caspase-2 to initiate apoptosis

Cell Death Differ. 2014 Mar;21(3):475-80. doi: 10.1038/cdd.2013.168. Epub 2013 Nov 29.


A recent report claimed that endoplasmic reticulum (ER) stress activates the ER trans-membrane receptor IRE1α, leading to increased caspase-2 levels via degradation of microRNAs, and consequently induction of apoptosis. This observation casts caspase-2 into a central role in the apoptosis triggered by ER stress. We have used multiple cell types from caspase-2-deficient mice to test this hypothesis but failed to find significant impact of loss of caspase-2 on ER-stress-induced apoptosis. Moreover, we did not observe increased expression of caspase-2 protein in response to ER stress. Our data strongly argue against a critical role for caspase-2 in ER-stress-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 2 / genetics
  • Caspase 2 / metabolism*
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Stress / physiology*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Thymocytes / enzymology
  • Thymocytes / metabolism
  • Up-Regulation
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Bak1 protein, mouse
  • Bax protein, mouse
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • CASP2 protein, human
  • Casp2 protein, mouse
  • Caspase 2
  • Cysteine Endopeptidases