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.
Di Certo
Maria Grazia
MG
Department of Experimental Medicine, Via Vetoio, Coppito 2, University of L'Aquila, 67100 L'Aquila, Italy.
Corbi
Nicoletta
N
Bruno
Tiziana
T
Iezzi
Simona
S
De Nicola
Francesca
F
Desantis
Agata
A
Ciotti
Maria Teresa
MT
Mattei
Elisabetta
E
Floridi
Aristide
A
Fanciulli
Maurizio
M
Passananti
Claudio
C
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*
C402637:AATF protein, human; D000951:Antigens, Neoplasm; D051017:Apoptosis Regulatory Proteins; C120897:MAGED1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014157:Transcription Factors