Title:The Tumor Suppressor Gene ARF as a Sensor of Oxidative Stress
Volume: 12
Issue: 6
Author(s): M. Liontos, I. S. Pateras, K. Evangelou and V. G. Gorgoulis
Affiliation:
Keywords:
ARF, DNA damage, free radicals, oxidative stress, ROS/RNS, signaling, radiation, nitric oxide, peroxynitrite anion, nitrosative stress, macromolecules, oxidation, UV light, cosmic rays, chemotherapeutics
Abstract: Oxidative stress as a result of either exogenous stimuli or cellular metabolism affects several cellular
processes such as proliferation, apoptosis, cell death and senescence. Consequently, it is implicated in the
pathogenesis of various human diseases like cancer, diabetes mellitus, atherosclerosis, neurodegenerative
diseases and aging. Oxidative stress is implicated in carcinogenesis either by directly provoking DNA damage
or through the regulation of intracellular signaling cascades. In both cases the cellular response to oxidative
stress is determined by the cellular context. ARF, the alternative protein product of the CDKN2A locus has
been recently recognized as a novel sensor of oxidative stress, in a β-catenin and Hsp70-mediated manner.
Since, improved understanding of cellular responses to oxidative stress may facilitate the design of novel
antineoplastic regimens, we herein review the mechanisms by which oxidative stress promotes
carcinogenesis, focusing on the role of ARF as a sensor of oxidative stress.
