| First Author | Gonzalez-Zuñiga M | Year | 2014 |
| Journal | Mol Cell | Volume | 56 |
| Issue | 1 | Pages | 163-73 |
| PubMed ID | 25219501 | Mgi Jnum | J:215541 |
| Mgi Id | MGI:5605605 | Doi | 10.1016/j.molcel.2014.08.013 |
| Citation | Gonzalez-Zuniga M, et al. (2014) c-Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimer's disease. Mol Cell 56(1):163-73 |
| abstractText | In Alzheimer's disease (AD), there is a decrease in neuronal gene expression induced by HDAC2 increase; however, the mechanisms involved are not fully elucidated. Here, we described how the tyrosine kinase c-Abl increases HDAC2 levels, inducing transcriptional repression of synaptic genes. Our data demonstrate that (1) in neurons, c-Abl inhibition with Imatinib prevents the AbetaO-induced increase in HDAC2 levels; (2) c-Abl knockdown cells show a decrease in HDAC2 levels, while c-Abl overexpression increases them; (3) c-Abl inhibition reduces HDAC2-dependent repression activity and HDAC2 recruitment to the promoter of several synaptic genes, increasing their expression; (4) c-Abl induces tyrosine phosphorylation of HDAC2, a posttranslational modification, affecting both its stability and repression activity; and (5) treatment with Imatinib decreases HDAC2 levels in a transgenic mice model of AD. Our results support the participation of the c-Abl/HDAC2 signaling pathway in the epigenetic blockade of gene expression in AD pathology. |
