TID1, a mammalian homologue of the drosophila tumor suppressor lethal(2) tumorous imaginal discs, regulates activation-induced cell death in Th2 cells.
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.
Syken
Josh
J
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, D2/544A, Boston, MA 02115-5701, USA.
Macian
Fernando
F
Agarwal
Suneet
S
Rao
Anjana
A
Münger
Karl
K
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005799:Genes, Dominant; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008969:Molecular Sequence Data; D018417:Th1 Cells; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
C120664:DNAJA3 protein, human; C485636:Dnaja3 protein, mouse; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases