Abstract
Cells in vivo do not act in isolation. Therefore, when attempting to predict the results of pharmaceutical modulation of the function of a protein, we must also take into account the non-cell-autonomous consequences of such modulation. Studies of caspase-8 initially indicated that it serves as the proximal enzyme in cellular self-destruction dictated through the extrinsic cell-death pathway. Later studies revealed that it also participates in mechanisms affecting cell growth and survival. This essay presents a brief account of a study indicating that, apart from functional changes that are cell autonomous, tissue-specific deletion of caspase-8 in mice also has non-cell-autonomous effects with consequences that might even be the opposite of the cell-autonomous ones.
| Original language | English |
|---|---|
| Pages (from-to) | 209-217 |
| Number of pages | 9 |
| Journal | Cytokine and Growth Factor Reviews |
| Volume | 19 |
| Issue number | 3-4 |
| DOIs | |
| State | Published - Jun 2008 |
| Externally published | Yes |
Bibliographical note
Funding Information:We are grateful to Dr. Irun Cohen for advice on the study of the role of caspase-8 expression in β-Langerhans cells in the development of diabetes in NOD mice, and to Dr. Steffen Jung for advice and help in studying the recovery of mice from L. monocytogenes infection. We thank for scientific editing. Work done in the laboratory of DW was supported in part by grants from Ares Trading S.A., Switzerland; a Center of Excellence Grant from the Flight Attendant Medical Research Institute (FAMRI); and the Kekst Family Center for Medical Genetics at The Weizmann Institute of Science.
Keywords
- Apoptosis
- Caspase-8
- Cell-autonomous
- TNF
- Therapy