Calcium Binding of ARC Mediates Regulation of Caspase 8 and Cell Death

Abstract

Apoptosis repressor with CARD (ARC) possesses the ability not only to block activation of caspase 8 but to modulate caspase-independent mitochondrial events associated with cell death. However, it is not known how ARC modulates both caspase-dependent and caspase-independent cell death.

Inhibition of Endoplasmic Reticulum Stress–Induced Apoptosis of Melanoma Cells by the ARC Protein

“…In addition, ER stress can cause calcium flux. The latter is conceivably bound by ARC and GRP78 and prevented from inducing apoptosis (9,25). Question marks at the arrow points indicate that more mechanisms may be found to involve in ER stress-induced apoptosis in melanoma cells, and accordingly more resistance mechanisms are yet to be discovered.…”

Apoptosis Repressor with Caspase Recruitment Domain Contributes to Chemotherapy Resistance by Abolishing Mitochondrial Fission Mediated by Dynamin-Related Protein-1

“…It can interact with Bax (16,17), inhibit cytochrome c release (18), and maintain mitochondrial membrane potential (19,20). Furthermore, ARC seems to be a calcium-binding protein and can suppress the intracellular Ca 2+ increase thereby blocking Ca 2+ -mediated apoptosis (21). In addition, our previous work shows that ARC is regulated by protein kinase CK2.…”

Transcription Factor Foxo3a Prevents Apoptosis by Regulating Calcium through the Apoptosis Repressor with Caspase Recruitment Domain

“…It has been shown that ARC is a calcium-binding protein and can suppress Ca 2ϩ -mediated apoptosis (53). This study demonstrated that ARC is present in the sarcoplasmic reticulum and participates in the regulation of mitochondrial Ca 2ϩ homeostasis by attenuating the release of [Ca 2ϩ ] SR induced by oxidative stress.…”

“…This study demonstrated that ARC is present in the sarcoplasmic reticulum and participates in the regulation of mitochondrial Ca 2ϩ homeostasis by attenuating the release of [Ca 2ϩ ] SR induced by oxidative stress. ARC requires the C terminus to bind to the calcium, and the deletion of the C terminus leads to the inability of ARC to bind to calcium (53). Intriguingly, the subcellular localization of ARC is controlled by the C terminus.…”