Conflicts of interest: None.
Type 1 inositol-1,4,5-trisphosphate receptor is a late substrate of caspases during apoptosis†
Article first published online: 15 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 113, Issue 8, pages 2775–2784, August 2012
How to Cite
Elkoreh, G., Blais, V., Béliveau, É., Guillemette, G. and Denault, J.-B. (2012), Type 1 inositol-1,4,5-trisphosphate receptor is a late substrate of caspases during apoptosis. J. Cell. Biochem., 113: 2775–2784. doi: 10.1002/jcb.24155
- Issue published online: 15 JUN 2012
- Article first published online: 15 JUN 2012
- Accepted manuscript online: 30 MAR 2012 08:55AM EST
- Manuscript Accepted: 22 MAR 2012
- Manuscript Received: 13 JAN 2012
- Canadian Institutes of Health Research (CIHR). Grant Number: MOP-86563
- Canadian Cancer Society (CCS). Grant Number: MOP-86757
- INOSITOL-1,4,5-TRISPHOSPHATE RECEPTOR;
- TEV PROTEASE
Apoptosis is characterized by the proteolytic cleavage of hundreds of proteins. One of them, the type 1 inositol-1,4,5-trisphosphate receptor (IP3R-1), a multimeric receptor located on the endoplasmic reticulum (ER) membrane that is critical to calcium homeostasis, was reported to be cleaved during staurosporine (STS) induced-apoptosis in Jurkat cells. Because the reported cleavage site separates the IP3 binding site from the channel moiety, its cleavage would shut down a critical signaling pathway that is common to several cellular processes. Here we show that IP3R-1 is not cleaved in 293 cells treated with STS, TNFα, Trail, or ultra-violet (UV) irradiation. Further, it is not cleaved in Hela or Jurkat cells induced to undergo apoptosis with Trail, TNFα, or UV. In accordance with previous reports, we demonstrate that it is cleaved in a Jurkat cell line treated with STS. However its cleavage occurs only after poly(ADP-ribose) polymerase (PARP), which cleavage is a hallmark of apoptosis, and p23, a poor caspase-7 substrate, are completely cleaved, suggesting that IP3R-1 is a relatively late substrate of caspases. Nevertheless, the receptor is fully accessible to proteolysis in cellulo by ectopically overexpressed caspase-7 or by the tobacco etch virus (TEV) protease. Finally, using recombinant caspase-3 and microsomal fractions enriched in IP3R-1, we show that the receptor is a poor caspase-3 substrate. Consequently, we conclude that IP3R-1 is not a key death substrate. J. Cell. Biochem. 113: 2775–2784, 2012. © 2012 Wiley Periodicals, Inc.