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Redox regulation of cellular activation
H Nakamura1, K Nakamura, J Yodoi
1Institute for Virus Research, Kyoto University, Japan.
Annual Review of Immunology
|January 1, 1997
Summary
Cellular redox status, maintained by thioredoxin (TRX), influences cell function and stress responses. Human TRX/Adult T cell leukemia-derived factor (ADF) has critical intracellular and extracellular roles in cell protection and gene regulation.
Area of Science:
- Cellular Biology
- Biochemistry
- Molecular Biology
Background:
- Cellular reduction/oxidation (redox) status is a key regulator of cellular functions, with oxidative stress inducing diverse cellular responses.
- Thioredoxin (TRX) is a crucial intracellular redox-regulating molecule maintaining cellular redox balance.
- Adult T cell leukemia-derived factor (ADF) has been identified as human TRX, a stress-inducible secreted protein.
Purpose of the Study:
- To elucidate the multifaceted roles of TRX/ADF in cellular responses to stress.
- To investigate the intracellular and extracellular functions of TRX/ADF.
- To explore the potential of redox regulation in understanding various diseases.
Main Methods:
- Characterization of TRX/ADF as human TRX.
- Analysis of extracellular functions, including cytoprotective and growth-promoting activities.
- Investigation of intracellular functions, such as translocation and gene expression regulation via Ref-1/APEX.
Main Results:
- TRX/ADF exhibits cytoprotective effects against oxidative stress-induced apoptosis.
- Extracellular TRX/ADF acts as an autocrine growth factor.
- Intracellular TRX/ADF regulates protein interactions and gene expression by translocating to the nucleus.
Conclusions:
- TRX/ADF is a vital regulator of cellular signaling in response to various stresses.
- Understanding TRX/ADF's regulatory roles and targets can illuminate intracellular signaling pathways.
- The concept of redox regulation is pivotal for understanding the pathogenesis of diseases like viral infections and cancer.