OTSU Kinya ≪Cardiovascular Medicine≫ “Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis.”
Publish J Clin Invest. 114:937-943 (2004)
The Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway regulates diverse cellular processes such as proliferation, differentiation, and apoptosis. Cardiac muscle-specific Raf-1-knockout (Raf CKO) mice demonstrated heart dysfunction. The Raf CKO mice showed a significant increase in the number of apoptotic cardiomyocytes. The expression level and activation of MEK1/2 or ERK showed no difference. The ablation of apoptosis signal-regulating kinase 1 (ASK1) rescued heart dysfunction. These results indicate that Raf-1 promotes cardiomyocyte survival through a MEK/ERK-independent mechanism.