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. 2014 Oct;45(10):3089-91.
doi: 10.1161/STROKEAHA.114.006348. Epub 2014 Aug 19.

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

Xiaoxi Wang  1 , Lei Pei  1 , Honglin Yan  1 , Zhongping Wang  1 , Na Wei  1 , Shan Wang  1 , Xin Yang  1 , Qing Tian  2 , Youming Lu  2
Affiliations

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

Xiaoxi Wang et al. Stroke. 2014 Oct.

Abstract

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.

Keywords: death-associated protein kinases; stroke.

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