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Targeted cleavage of signaling proteins by caspase 3 inhibits T cell receptor signaling in anergic T cells.

ABSTRACT: T cell receptor (TCR) engagement in the absence of costimulation induces the calcium-dependent upregulation of a program of gene expression that leads to the establishment of T cell anergy. Casp3 is one of the genes activated during anergy induction. Here we show that caspase 3 is required for the induction of T cell unresponsiveness. Suboptimal T cell stimulation induced caspase 3 activation, which did not result in cell death. Furthermore, caspase 3-deficient T cells showed impaired responses to anergizing stimuli. In anergic T cells, activated caspase 3 associated to the plasma membrane, where it cleaved and inactivated proteins such as the Grb2-related adaptor downstream of shc (GADS) and the guanine-nucleotide exchange factor Vav1, causing a blockade in TCR signaling. Our results identify a role for caspase 3 in nonapoptotic T cells and support that caspase 3-dependent proteolytic inactivation of signaling proteins is essential to maintain T cell tolerance.

SUBMITTER: Puga I

PROVIDER: S-EPMC2630799 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Targeted cleavage of signaling proteins by caspase 3 inhibits T cell receptor signaling in anergic T cells.

Puga Irene I Rao Anjana A Macian Fernando F

Immunity 20080801 2

T cell receptor (TCR) engagement in the absence of costimulation induces the calcium-dependent upregulation of a program of gene expression that leads to the establishment of T cell anergy. Casp3 is one of the genes activated during anergy induction. Here we show that caspase 3 is required for the induction of T cell unresponsiveness. Suboptimal T cell stimulation induced caspase 3 activation, which did not result in cell death. Furthermore, caspase 3-deficient T cells showed impaired responses ...[more]

PMID: 18701083

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