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Publication : Intervention of death-associated protein kinase 1-p53 interaction exerts the therapeutic effects against stroke.

First Author  Wang X Year  2014
Journal  Stroke Volume  45
Issue  10 Pages  3089-91
PubMed ID  25139875 Mgi Jnum  J:382515
Mgi Id  MGI:8314575 Doi  10.1161/STROKEAHA.114.006348
Citation  Wang X, et al. (2014) Intervention of death-associated protein kinase 1-p53 interaction exerts the therapeutic effects against stroke. Stroke 45(10):3089-91
abstractText  BACKGROUND AND PURPOSE: Death-associated protein kinase 1 (DAPK1) interacts with the tumor suppressor gene p53 via a direct binding of a death domain of DAPK1 to a DNA-binding motif (DM) of p53 (p53DM) and converges multiple cell death pathways in stroke. The goals of this study are to determine whether disruption of DAPK1-p53 interaction is therapeutically effective against stroke. METHODS: We synthesized a membrane-permeable p53DM peptide (Tat-p53DM) and tested the therapeutic effects of Tat-p53DM in a mouse model with stroke. RESULTS: We showed that Tat-p53DM blocked DAPK1-p53 interaction in brain cells in vivo. When administered 6 hours after stroke onset in adult male mice, Tat-p53DM was still therapeutically effective against brain damages and improved neurological functions. CONCLUSIONS: DAPK1-p53 interaction is a preferred target for therapeutic intervention of stroke.
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