title: Cisplatin enhances interaction between p66Shc and HSP27: its role in reorganization of the actin cytoskeleton in renal proximal tubule cells.
abstract: OBJECTIVE
  Cisplatin nephrotoxicity includes early activation of the pro-apoptotic p66Shc and disorganization of the actin cytoskeleton, integrity which is regulated by heat-shock protein-27 (Hsp27). Here we determined the potential role of p66Shc in abrogating the Hsp27 function.
  
  
  METHODS
  Effects of p66Shc knockdown and Hsp27 overexpression on F-actin stress fibers after cisplatin treatment were visualized by phalloidin staining. Binding of p66Shc to Hsp27 after cisplatin treatment was determined by immunoprecipitation in cell and tissue lysates. The role of p66Shc and its Ser36 phosphorylation in Hsp27 binding was assessed by overexpressing it or mutating its Ser36 residue.
  
  
  RESULTS
  Knockdown of p66Shc and overexpression of Hsp27 ameliorated cisplatin-mediated collapse of the actin cytoskeleton. Further studies revealed that p66Shc binds Hsp27 after treatment with cisplatin that requires Ser36 phosphorylation of p66Shc.
  
  
  CONCLUSIONS
  We propose a novel function of p66Shc that, through interacting with Hsp27, accelerates cisplatin-dependent disruption of the actin cytoskeleton.
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS, USA. iarany@umc.edu
authors.forename: Istvan
authors.initials: I
authors.lastname: Arany
authors.forename: Jeb S
authors.initials: JS
authors.lastname: Clark
authors.forename: Dustin K
authors.initials: DK
authors.lastname: Reed
authors.forename: Istvan
authors.initials: I
authors.lastname: Ember
authors.forename: Luis A
authors.initials: LA
authors.lastname: Juncos
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015153:Blotting, Western; D002945:Cisplatin / Q000633:toxicity*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D000970:Antineoplastic Agents; D055551:HSP27 Heat-Shock Proteins; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D002945:Cisplatin