Back to Search
Start Over
DAPK1-p53 Interaction Converges Necrotic and Apoptotic Pathways of Ischemic Neuronal Death.
- Source :
-
Journal of Neuroscience . 5/7/2014, Vol. 34 Issue 19, p6546-6556. 11p. - Publication Year :
- 2014
-
Abstract
- Necrosis and apoptosis are two distinct types of mechanisms that mediate ischemic injury. But a signaling point of convergence between them has yet to be identified. Here, we show that activated death-associated protein kinase 1 (DAPK1), phosphorylates p53 at serine-23 (pS23) via a direct binding of DAPK1 death domain (DAPK1DD) to the DNA binding motif of p53 (p53DM). We uncover that the pS23 acts as a functional version of p53 and mediates necrotic and apoptotic neuronal death; in the nucleus, pS23 induces the expression of proapoptotic genes, such as Bax, whereas in the mitochondrial matrix, pS23 triggers necrosis via interaction with cyclophilin D (CypD) in cultured cortical neurons from mice. Deletion of DAPK1DD (DAPK1DDΔ) or application of Tat-p53DM that interrupts DAPK1-p53 interaction blocks these dual pathways of pS23 actions in mouse cortical neurons. Thus, the DAPK1-p53 interaction is a signaling point of convergence of necrotic and apoptotic pathways and is a desirable target for the treatment of ischemic insults. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02706474
- Volume :
- 34
- Issue :
- 19
- Database :
- Academic Search Index
- Journal :
- Journal of Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 95949637
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.5119-13.2014