NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death.

Neurotrophin receptor-interacting MAGE homolog (NRAGE) has been recently identified as a cell-death inducer, involved in molecular events driving cells through apoptotic networks during neuronal development. Recently, we have focused on the functional role of Che-1, also known as apoptosis-antagonizing transcription factor (AATF), a protein involved in cell cycle control and ...
gene transcription. Increasing evidence suggests that Che-1 is involved in apoptotic signalling in neural tissues. In cortical neurons Che-1 exhibits an anti-apoptotic activity, protecting cells from neuronal damage induced by amyloid beta-peptide. Here, we report that Che-1 interacts with NRAGE and that an EGFP-NRAGE fusion protein inhibits nuclear localization of Che-1, by sequestering it within the cytoplasmic compartment. Furthermore, NRAGE overexpression downregulates endogenous Che-1 by targeting it for proteasome-dependent degradation. Finally, we propose that Che-1 is a functional antagonist of NRAGE, because its overexpression completely reverts NRAGE-induced cell-death.
Mesh Terms:
Animals, Antigens, Neoplasm, Apoptosis Regulatory Proteins, Cell Death, Cell Nucleus, Hela Cells, Humans, Mice, NIH 3T3 Cells, Neoplasm Proteins, Protein Binding, Protein Processing, Post-Translational, Protein Transport, Repressor Proteins, Transcription Factors
J. Cell. Sci.
Date: Jun. 01, 2007
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