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c‐Abl modulates AICD dependent cellular responses: Transcriptional induction and apoptosis
Author(s) -
Vázquez Mary C.,
Vargas Lina M.,
Inestrosa Nibaldo C.,
Alvarez Alejandra R.
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21743
Subject(s) - signal transducing adaptor protein , kinase , abl , microbiology and biotechnology , biology , gene isoform , apoptosis , transcription factor , signal transduction , chemistry , gene , biochemistry , tyrosine kinase
Abstract APP intracellular domain (AICD) has been proposed as a transcriptional inductor that moves to the nucleus with the adaptor protein Fe65 and regulates transcription. The two proteins, APP and Fe65, can be phosphorylated by c‐Abl kinase. Neprilysin has been proposed as a target gene for AICD. We found that AICD expression is decreased by treatment with STI‐571, a c‐Abl inhibitor, suggesting a modulation of AICD transcription by c‐Abl kinase. We observed interaction between c‐Abl kinase, the AICD fragment and the Fe65 adaptor protein. In addition, STI‐571 reduces apoptosis in APPSw, and the apoptotic response induced by Fe65 over‐expression was inhibited by with the expression of a kinase dead (KD) c‐Abl and enhanced by over‐expression of WT‐c‐Abl. However, in the APPSw cells, the ability of the KD‐c‐Abl to protect against Fe65 was reduced. Finally, in APPSw clone, we detected higher trans‐activation of the pro‐apoptotic p73 isoform, TAp73 promoter. Our results show that c‐Abl modulates AICD dependent cellular responses, transcriptional induction as well as the apoptotic response, which could participate in the onset and progression of the neurodegenerative pathology, observed in Alzheimer's disease (AD). J. Cell. Physiol. 220: 136–143, 2009. © 2009 Wiley‐Liss, Inc.