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Type 1 inositol-1,4,5-trisphosphate receptor is a late substrate of caspases during apoptosis

Ghadi Elkoreh1, Véronique Blais, Eric Béliveau

  • 1Faculty of Medicine and Health Sciences, Department of Pharmacology, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke QC J1H 5N4, Canada.

Journal of Cellular Biochemistry
|April 5, 2012
PubMed

Insights

Type 1 inositol-1,4,5-trisphosphate receptor (IP(3) R-1) is not a key substrate during apoptosis. While cleaved in some cells, it occurs late and is a poor substrate for key caspases.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis involves protein cleavage, including the IP(3) R-1 receptor crucial for calcium homeostasis.
  • Previous studies suggested IP(3) R-1 cleavage during staurosporine-induced apoptosis in Jurkat cells.

Purpose of the Study:

  • To investigate the cleavage of IP(3) R-1 during apoptosis across different cell types and stimuli.
  • To determine the timing and caspase dependency of IP(3) R-1 cleavage.

Main Methods:

  • Inducing apoptosis in various cell lines (293, Hela, Jurkat) using staurosporine, TNFα, Trail, and UV irradiation.
  • Western blot analysis to detect cleavage of IP(3) R-1, PARP, and p23.
  • In vitro assays using recombinant caspase-3 and microsomal fractions.

Main Results:

  • IP(3) R-1 was not cleaved in 293, Hela, or Jurkat cells treated with TNFα, Trail, or UV.
  • Cleavage of IP(3) R-1 was observed in Jurkat cells treated with staurosporine, but only after PARP and p23 cleavage.
  • Recombinant caspase-3 showed poor cleavage of IP(3) R-1 in vitro.

Conclusions:

  • IP(3) R-1 is not a universal or early substrate during apoptosis.
  • Its late cleavage and poor substrate efficiency for caspase-3 suggest it is not a key death substrate.

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