NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death
Author:
Di Certo Maria Grazia12, Corbi Nicoletta3, Bruno Tiziana4, Iezzi Simona14, De Nicola Francesca14, Desantis Agata13, Ciotti Maria Teresa2, Mattei Elisabetta2, Floridi Aristide14, Fanciulli Maurizio45, Passananti Claudio35
Affiliation:
1. Department of Experimental Medicine, Via Vetoio, Coppito 2, University of L'Aquila, 67100 L'Aquila, Italy 2. Istituto di Neurobiologia e Medicina Molecolare, CNR, c/o EBRI, Via del Fosso di Fiorano 64, 00143 Rome, Italy 3. Istituto di Biologia e Patologia Molecolari, CNR, c/o Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy 4. Laboratory “B”, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy 5. AIRC-Roman Oncogenomic Center (ROC), Via delle Messi d'Oro 156, 00158 Rome, Italy
Abstract
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 β-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.
Publisher
The Company of Biologists
Reference30 articles.
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