Open AccessApoptosis repressor with caspase recruitment domain, a multifunctional modulator of cell death
Author(s) -
LudwigGalezowska Agnieszka H.,
Flanagan Lorna,
Rehm Markus
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01221.x
Subject(s) - microbiology and biotechnology , apoptosis , arc (geometry) , biology , programmed cell death , caspase , repressor , transcription factor , gene , genetics , geometry , mathematics
• Introduction• ARC identification and tissue‐specific expression• The molecular structure of ARC• (Patho)physiology and ARC expression‐ Physiological role and expression of ARC in cardiac and skeletal muscle tissue‐ Physiological role and expression of ARC in brain tissue‐ ARC expression and localization in cancer• Regulation of ARC protein levels by gene transcription and protein degradation• Multi‐functionality of ARC in apoptosis inhibition‐ Extrinsic apoptosis initiation‐ Intrinsic apoptosis initiation and the mitochondrial apoptosis pathway• Concluding commentsApoptosis 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 Ca 2+ 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.