TY - JOUR
T1 - NRAGE associates with the anti-apoptopic factor Che-1 and regulates its degradation to induce cell death
AU - Di Certo, Maria Grazia
AU - Corbi, Nicoletta
AU - Bruno, Tiziana
AU - Iezzi, Simona
AU - De Nicola, Francesca
AU - Desantis, Agata
AU - Ciotti, Maria Theresa
AU - Mattel, Elisabetta
AU - Floridi, Aristide
AU - Fanciulli, Maurizio
AU - Passananti, Claudio
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
KW - AATF
KW - Apoptosis
KW - Che-1
KW - MAGE
KW - Neural cell-death
KW - NRAGE
KW - Ubiquitin
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UR - http://www.scopus.com/inward/citedby.url?scp=34250802643&partnerID=8YFLogxK
U2 - 10.1242/jcs.03454
DO - 10.1242/jcs.03454
M3 - Article
C2 - 17488777
AN - SCOPUS:34250802643
VL - 120
SP - 1852
EP - 1858
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 11
ER -