title: Intervention of death-associated protein kinase 1-p53 interaction exerts the therapeutic effects against stroke.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., N.W., S.W., X.Y., Q.T., Y.L.); Department of Physiology and Pathophysiology, Jiujiang University, Jiujiang, China (Z.W.); and Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., Z.W., N.W., S.W., X.Y., Y.L.).
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Wang
authors.affiliation: From the Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., N.W., S.W., X.Y., Q.T., Y.L.); Department of Physiology and Pathophysiology, Jiujiang University, Jiujiang, China (Z.W.); and Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., Z.W., N.W., S.W., X.Y., Y.L.).
authors.forename: Lei
authors.initials: L
authors.lastname: Pei
authors.affiliation: From the Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., N.W., S.W., X.Y., Q.T., Y.L.); Department of Physiology and Pathophysiology, Jiujiang University, Jiujiang, China (Z.W.); and Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., Z.W., N.W., S.W., X.Y., Y.L.).
authors.forename: Honglin
authors.initials: H
authors.lastname: Yan
authors.affiliation: From the Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., N.W., S.W., X.Y., Q.T., Y.L.); Department of Physiology and Pathophysiology, Jiujiang University, Jiujiang, China (Z.W.); and Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., Z.W., N.W., S.W., X.Y., Y.L.).
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Wang
authors.affiliation: From the Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., N.W., S.W., X.Y., Q.T., Y.L.); Department of Physiology and Pathophysiology, Jiujiang University, Jiujiang, China (Z.W.); and Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., Z.W., N.W., S.W., X.Y., Y.L.).
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: From the Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., N.W., S.W., X.Y., Q.T., Y.L.); Department of Physiology and Pathophysiology, Jiujiang University, Jiujiang, China (Z.W.); and Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., Z.W., N.W., S.W., X.Y., Y.L.).
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: From the Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., N.W., S.W., X.Y., Q.T., Y.L.); Department of Physiology and Pathophysiology, Jiujiang University, Jiujiang, China (Z.W.); and Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., Z.W., N.W., S.W., X.Y., Y.L.).
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: From the Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., N.W., S.W., X.Y., Q.T., Y.L.); Department of Physiology and Pathophysiology, Jiujiang University, Jiujiang, China (Z.W.); and Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., Z.W., N.W., S.W., X.Y., Y.L.). tianq@hust.edu.cn lym@hust.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: From the Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., N.W., S.W., X.Y., Q.T., Y.L.); Department of Physiology and Pathophysiology, Jiujiang University, Jiujiang, China (Z.W.); and Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China (X.W., L.P., H.Y., Z.W., N.W., S.W., X.Y., Y.L.). tianq@hust.edu.cn lym@hust.edu.cn.
authors.forename: Youming
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D064550:Death-Associated Protein Kinases / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D020521:Stroke / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D054322:tat Gene Products, Human Immunodeficiency Virus; C579106:Dapk1 protein, mouse; D064550:Death-Associated Protein Kinases
keywords: death-associated protein kinases; stroke