CSF : Vol. 28 (2003) , No. 1 pp.23-29

Roles of MAPKKK ASK1 in Stress-Induced Cell Death

Kohsuke Takeda¹⁾²⁾³⁾, Atsushi Matsuzawa²⁾³⁾, Hideki Nishitoh¹⁾²⁾³⁾ and Hidenori Ichijo¹⁾²⁾³⁾

1) Laboratory of Cell Signaling, Graduate School, Tokyo Medical and Dental University
2) Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo
3) Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation

ABSTRACT. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein (MAP) kinase kinase kinase that activates the c-Jun N-terminal kinase (JNK) and p38 MAP kinase signaling cascades. Recent findings from analyses of ASK1-deficient mice have revealed that ASK1 is required for apoptosis induced by oxidative stress, TNF and endoplasmic reticulum (ER) stress. In addition, several lines of evidence have suggested that ASK1 has diverse functions in the decision of cell fate beyond its pro-apoptotic activity. Thus, ASK1 appears to be a pivotal component not only in stress-induced cell death but also in a broad range of biological activities in order for cells to adapt to or oppose various stresses.

Key words: MAPKKK/ ASK1/ JNK/ p38/ apoptosis