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Immunophilins in protein folding and immunosuppression
D A Fruman1, S J Burakoff, B E Bierer
1Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Summary
Immunosuppressive drugs like cyclosporin A and FK506 reveal key proteins called immunophilins. These immunophilins are crucial for lymphocyte signaling and immune suppression.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Lymphocyte activation involves complex signal transduction pathways from the cell membrane to the nucleus.
- Immunosuppressive drugs are valuable tools for dissecting these signaling cascades.
- Cyclosporin A (CsA), FK506, and rapamycin are well-studied immunosuppressants.
Purpose of the Study:
- To review the endogenous functions of immunophilins.
- To discuss the role of immunophilins in mediating immunosuppression.
- To highlight immunophilins as key molecules in lymphocyte signal transduction.
Main Methods:
- Literature review of studies on immunosuppressants and their binding proteins.
- Identification and classification of immunophilin families.
- Analysis of the mechanisms of action for CsA, FK506, and rapamycin.
Main Results:
- Two major classes of immunosuppressant-binding proteins, immunophilins, have been identified.
- The cyclophilin family binds CsA.
- The FK506-binding protein (FKBP) family binds FK506 and rapamycin.
Conclusions:
- Immunophilins play critical roles in both normal lymphocyte function and immunosuppression.
- Understanding immunophilin function provides insights into immune regulation.
- Targeting immunophilins offers therapeutic potential for immune-related diseases.