| CAML regulates Bim-dependent thymocyte death. | |
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MedLine Citation:
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PMID: 20300112 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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C E Edgar; L D Lindquist; D L McKean; A Strasser; R J Bram |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-03-19 |
Journal Detail:
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Title: Cell death and differentiation Volume: 17 ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-13 Completed Date: 2011-01-04 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 1566-76 Citation Subset: IM |
Affiliation:
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Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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genetics,
metabolism* Animals Antigens, CD95 / metabolism Apoptosis* Apoptosis Regulatory Proteins / metabolism* Etoposide / pharmacology Membrane Proteins / metabolism* Mice Proto-Oncogene Proteins / metabolism* Reactive Oxygen Species / metabolism T-Lymphocytes / cytology*, immunology Tumor Suppressor Protein p53 / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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2R01AI074320/AI/NIAID NIH HHS; R01 AI074320-09/AI/NIAID NIH HHS; R56 AI074320-06A1/AI/NIAID NIH HHS; T32 AI07425-14/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Antigens, CD95; 0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/Caml protein, mouse; 0/Fas protein, mouse; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/Reactive Oxygen Species; 0/Tumor Suppressor Protein p53; 33419-42-0/Etoposide |
| Comments/Corrections | |
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