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

Maria Grazia Di Certo, Nicoletta Corbi, Tiziana Bruno, Simona Iezzi, Francesca De Nicola, Agata Desantis, Maria Theresa Ciotti, Elisabetta Mattel, Aristide Floridi, Maurizio Fanciulli, Claudio Passananti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1852-1858
Number of pages7
JournalJournal of Cell Science
Volume120
Issue number11
DOIs
Publication statusPublished - Jun 1 2007

Keywords

  • AATF
  • Apoptosis
  • Che-1
  • MAGE
  • Neural cell-death
  • NRAGE
  • Ubiquitin

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'NRAGE associates with the anti-apoptopic factor Che-1 and regulates its degradation to induce cell death'. Together they form a unique fingerprint.

Cite this