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Stress signals for apoptosis: ceramide and c-Jun kinase
1Laboratory of Signal Transduction, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Abstract:
Mammalian systems respond to environmental stress by either adapting or undergoing programmed cell death. While there is general agreement that the caspase family of proteases serve as the effectors of the apoptotic death response, the signaling apparatus involved in the decision to activate the caspase system is less clear. In the past few years, the sphingomyelin and c-Jun Kinase (JNK)/Stress-activated Protein Kinase (SAPK) pathways have been linked to the death response in many cellular systems. These signaling systems are found throughout the animal kingdom, and ceramide signaling is conserved through yeast. Since yeast do not undergo apoptosis, the sphingomyelin pathway appears evolutionarily older than the caspase-mediated death programs. While recent reviews by several groups have broadly surveyed ceramide signaling in apoptosis, this paper examines the role of sphingomyelinases and the JNK/SAPK pathway in coordinate signaling of apoptosis.
Insights
Environmental stress triggers adaptation or cell death. This study explores how sphingomyelin and c-Jun Kinase (JNK)/Stress-activated Protein Kinase (SAPK) pathways coordinate apoptosis signaling, revealing an evolutionarily older sphingomyelin pathway.
Area of Science:
- Cellular biology
- Biochemistry
- Molecular biology
Background:
- Mammalian cells adapt to or undergo programmed cell death in response to environmental stress.
- Caspase proteases are known effectors of apoptosis, but the upstream signaling pathways remain unclear.
- The sphingomyelin and c-Jun Kinase (JNK)/Stress-activated Protein Kinase (SAPK) pathways are increasingly implicated in stress-induced cell death.
Purpose of the Study:
- To investigate the coordinated roles of sphingomyelinases and the JNK/SAPK pathway in apoptosis signaling.
- To explore the evolutionary history of ceramide signaling in relation to apoptosis.
Main Methods:
- Review of existing literature on sphingomyelin and JNK/SAPK signaling in apoptosis.
- Comparative analysis of ceramide signaling conservation across species, including yeast.
- Examination of the interplay between sphingomyelinases and JNK/SAPK in apoptotic pathways.
Main Results:
- The sphingomyelin pathway, involving ceramide signaling, is conserved through yeast and appears evolutionarily older than caspase-mediated apoptosis.
- Both sphingomyelinases and the JNK/SAPK pathway are linked to stress-induced cell death.
- These pathways likely play a coordinated role in initiating the apoptotic response.
Conclusions:
- The sphingomyelin pathway and JNK/SAPK pathway are key components in the decision-making process for initiating apoptosis.
- Understanding these upstream signals is crucial for elucidating the mechanisms of programmed cell death.
- Ceramide signaling provides an evolutionarily ancient link to stress responses that precede the evolution of apoptosis.