TID1, a mammalian homologue of the drosophila tumor suppressor lethal(2) tumorous imaginal discs, regulates activation-induced cell death in Th2 cells

Josh Syken, Fernando Macian, Suneet Agarwal, Anjana Rao, Karl Münger

Research output: Contribution to journalArticle

20 Scopus citations

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-1 S 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.

Original languageEnglish (US)
Pages (from-to)4636-4641
Number of pages6
JournalOncogene
Volume22
Issue number30
DOIs
StatePublished - Jul 24 2003

Keywords

  • Apoptosis
  • DnaJ protein
  • T cells
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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