Stress-responsive protein kinases in redox-regulated apoptosis signaling

Atsushi Matsuzawa, Hidenori Ichijo

Research output: Contribution to journalReview articlepeer-review

249 Citations (Scopus)


Both extra- and intracellular stimuli elicit a wide variety of responses, such as cell survival, proliferation, differentiation, and apoptosis, through regulation of cell signaling. Recent studies have revealed that stress-responsive signal transduction pathways are strictly regulated by the intracellular redox state. The redox state of the cell is a consequence of the precise balance between the levels of oxidizing and reducing equivalents, such as reactive oxygen species (ROS) and endogenous antioxidants. The generation of ROS fluctuates in response to alterations of both external and internal environment and, in turn, triggers specific signaling cascades, including mitogen-activated protein kinases, which determine cell survival or cell death. This review focuses on the regulatory mechanisms of stress-responsive protein kinases and their involvement in oxidative stress-induced apoptosis. It also provides recent findings on the molecular mechanisms by which redox signaling cross-talks with stress-responsive protein kinase cascades.

Original languageEnglish
Pages (from-to)472-481
Number of pages10
JournalAntioxidants and Redox Signaling
Issue number3-4
Publication statusPublished - 2005 Mar


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