title: NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death.
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 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.
authors.affiliation: Department of Experimental Medicine, Via Vetoio, Coppito 2, University of L'Aquila, 67100 L'Aquila, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Di Certo
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Corbi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bruno
authors.forename: Simona
authors.initials: S
authors.lastname: Iezzi
authors.forename: Francesca
authors.initials: F
authors.lastname: De Nicola
authors.forename: Agata
authors.initials: A
authors.lastname: Desantis
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mattei
authors.forename: Aristide
authors.initials: A
authors.lastname: Floridi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fanciulli
authors.forename: Claudio
authors.initials: C
authors.lastname: Passananti
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism*; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: C402637:AATF protein, human; D000951:Antigens, Neoplasm; D051017:Apoptosis Regulatory Proteins; C120897:MAGED1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors