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Modulation of IP₃ receptor stability and its implication in cell death and disease

Journal Contribution - Journal Article

Ca2+ is a ubiquitous and versatile second messenger, which is important for processes like cell death and survival. Intracellular Ca2+ dynamics are tightly controlled by several Ca2+-transport systems. The main intracellular Ca2+-release channel is inositol 1,4,5-trisphosphate (IP3) receptor (IP3R), which is responsible for the Ca2+ flux from the endoplasmic reticulum. IP3R dysfunction has been implicated in various pathological conditions including cancer and neurodegenerative diseases. Hence, IP3Rs function at the common cross-point of different pro-survival and cell-death signaling pathways and are targeted by several proteins. A number of protein modifications directly impact IP3R gating and thus Ca2+-flux properties. Yet, several regulating mechanisms emerged to regulate total IP3R levels by altering IP3R stability and turnover through proteasomal degradation and protease cleavage. In the present review, we will highlight the mechanisms and the impact of (i) IP3R ubiquitination and the following proteasomal degradation and (ii) IP3R cleavage by two major classes of proteases, namely caspases and calpains.
Journal: Messenger
ISSN: 2167-955X
Volume: 6
Pages: 9 - 21
Publication year:2018
Accessibility:Open