CAML regulates Bim-dependent thymocyte death
- Author(s)
- Edgar, CE; Lindquist, LD; McKean, DL; Strasser, A; Bram, RJ;
- Details
- Publication Year 2010-10,Volume 17,Issue #10,Page 1566-1576
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Publication Type
- Journal Article
- Abstract
- Appropriate control of apoptosis during T lymphocyte differentiation is critical for destruction of T cells bearing potentially autoreactive or useless immuno-receptors and for survival of those T cells bearing antigen receptors that may recognize foreign proteins. Despite the well-established importance of thymocyte survival, the exact signals regulating thymocyte apoptosis have not been fully elucidated. Here, we show that thymocytes lacking the endoplasmic reticulum protein calcium-modulating cyclophilin ligand (CAML) failed to undergo normal T-cell development and exhibited dramatically increased rates of apoptosis. In vitro, CAML-deficient thymocytes accumulated high levels of reactive oxygen species (ROS) and underwent abnormally accelerated death in response to several cytotoxic stimuli, including treatment with etoposide, cytokine deprivation, or Fas ligation. Although neither p53 deletion nor loss of Fas rescued the survival and continued development of CAML-deficient thymocytes, removal of the pro-apoptotic BH3-only Bcl-2 family member Bim significantly restored their survival. This work reveals CAML to be a critically important regulator of ROS- and Bim-dependent thymocyte death. Cell Death and Differentiation (2010) 17, 1566-1576; doi:10.1038/cdd.2010.30; published online 19 March 2010
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- FAMILY-MEMBER BIM; MODULATING CYCLOPHILIN LIGAND; PROAPOPTOTIC PROTEIN BIM; T-CELL APOPTOSIS; NEGATIVE SELECTION; BCL-2 FAMILY; BH3-ONLY PROTEINS; AUTOREACTIVE THYMOCYTES; BH3 DOMAIN; MICE
- Publisher's Version
- https://doi.org/10.1038/cdd.2010.30
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-10-01 12:00:00