Unknown

Dataset Information

0

Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis.


ABSTRACT: Fas receptor is a member of the tumor necrosis factor-alpha family of death receptors that mediate physiologic apoptotic signaling. To investigate the molecular mechanisms regulating calcium mobilization during Fas-mediated apoptosis, we have analyzed the sequential steps leading to altered calcium homeostasis and cell death in response to activation of the Fas receptor. We show that Fas-mediated apoptosis requires endoplasmic reticulum-mediated calcium release in a mechanism dependent on phospholipase C-gamma1 (PLC-gamma1) activation and Ca2+ release from inositol 1,4,5-trisphosphate receptor (IP3R) channels. The kinetics of Ca2+ release were biphasic, demonstrating a rapid elevation caused by PLC-gamma1 activation and a delayed and sustained increase caused by cytochrome c binding to IP3R. Blocking either phase of Ca2+ mobilization was cytoprotective, highlighting PLC-gamma1 and IP3R as possible therapeutic targets for disorders associated with Fas signaling.

SUBMITTER: Wozniak AL 

PROVIDER: S-EPMC2064670 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis.

Wozniak Ann L AL   Wang Xinmin X   Stieren Emily S ES   Scarbrough Shelby G SG   Elferink Cornelis J CJ   Boehning Darren D  

The Journal of cell biology 20061127 5


Fas receptor is a member of the tumor necrosis factor-alpha family of death receptors that mediate physiologic apoptotic signaling. To investigate the molecular mechanisms regulating calcium mobilization during Fas-mediated apoptosis, we have analyzed the sequential steps leading to altered calcium homeostasis and cell death in response to activation of the Fas receptor. We show that Fas-mediated apoptosis requires endoplasmic reticulum-mediated calcium release in a mechanism dependent on phosph  ...[more]

Similar Datasets

| S-EPMC3017677 | biostudies-literature
| S-EPMC4979459 | biostudies-literature
| S-EPMC8206108 | biostudies-literature
| S-EPMC5968115 | biostudies-literature
| S-EPMC10507440 | biostudies-literature
| S-EPMC6062323 | biostudies-literature
| S-EPMC5454937 | biostudies-literature
| S-EPMC2899892 | biostudies-literature
| S-EPMC2192035 | biostudies-literature
| S-EPMC4178181 | biostudies-literature