Apoptosis repressor with caspase recruitment domain, a multifunctional modulator of cell death

Apoptosis repressor with caspase recruitment domain (ARC) is a highly potent and multifunctional inhibitor of apoptosis that is physiologically expressed predominantly in post-mitotic cells such as cardiomyocytes, skeletal muscle cells and neurons. ARC was also found to be up-regulated in many forms of malignant tumours. ARC impairs the cellular apoptotic responsiveness to a wide range of stresses and insults, including extrinsic apoptosis initiation via death receptor ligands, dysregulation of cellular Ca2+ homeostasis and endoplasmatic reticulum (ER) stress, genotoxic drugs, ionizing radiation, oxidative stress and hypoxia. ARC is subject to both transcriptional and post-translational regulation and exhibits its function through a multitude of molecular interactions with upstream transducers of apoptosis signals. This review summarizes, structures and comments on the published knowledge regarding ARC and its roles in modulating apoptotic cell death responsiveness in physiological and pathophysiological contexts.