Abstract |
We previously described two human DnaJ proteins, hTid-1L and hTid-1S, which are derived from alternative splicing of the TID1 gene, the human homologue of the Drosophila tumor suppressor lethal(2) tumorous imaginal discs, and showed that hTid-1L promoted while hTid-1S antagonized apoptosis. There are two subsets of helper T cells, Th1 and Th2, of which Th2 cells are significantly less prone to apoptosis induced by stimulation through the T-cell receptor. This apoptotic process is known as activation-induced cell death (AICD). The molecular basis for the differential susceptibility of Th1 and Th2 cells to AICD is not known. Here we show that the antiapoptotic variant, Tid-1S, is selectively induced in murine Th2 cells following activation. Expression of a dominant-negative mutant of hTid-1S in a Th2 cell line strikingly enhanced activation of caspase 3 in response to CD3 stimulation, and caused the cells to become sensitive to AICD. Hence, the accumulation of Tid-1S in Th2 cells following activation represents a novel mechanism that may contribute to the induction of apoptosis resistance during the activation of Th2 cells.
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Authors | Josh Syken, Fernando Macian, Suneet Agarwal, Anjana Rao, Karl Münger |
Journal | Oncogene
(Oncogene)
Vol. 22
Issue 30
Pg. 4636-41
(Jul 24 2003)
ISSN: 0950-9232 [Print] England |
PMID | 12879007
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- DNAJA3 protein, human
- Dnaja3 protein, mouse
- HSP40 Heat-Shock Proteins
- Heat-Shock Proteins
- CASP3 protein, human
- Casp3 protein, mouse
- Caspase 3
- Caspases
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Topics |
- Amino Acid Sequence
- Animals
- Apoptosis
- Caspase 3
- Caspases
(metabolism)
- Cell Death
- Cell Differentiation
- Cell Line
- Electrophoresis, Polyacrylamide Gel
- Genes, Dominant
- HSP40 Heat-Shock Proteins
- Heat-Shock Proteins
(metabolism, physiology)
- Humans
- Jurkat Cells
- Mice
- Molecular Sequence Data
- Th1 Cells
- Th2 Cells
(metabolism, pathology)
- Time Factors
- Transfection
- Up-Regulation
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