title: Zyxin is a novel interacting partner for SIRT1.
abstract: BACKGROUND
  SIRT1 is a mammalian homologue of NAD+-dependent deacetylase sirtuin family. It regulates longevity in several model organisms and is involved with cell survival, differentiation, metabolism among other processes in mammalian cells. SIRT1 modulates functions of various key targets via deacetylation. Recent studies have revealed SIRT1 protects neurons from axonal degeneration or neurodegeneration. Further, SIRT1 null mice exhibit growth retardation and developmental defects, suggesting its critical roles in neurons and development.
  
  
  RESULTS
  To identify novel binding partners for SIRT1 in the central nervous system, we performed yeast two-hybrid screening on human fetal brain cDNA library and found that zyxin is a possible binding partner. SIRT1 and zyxin transcript were both preferentially expressed in developmental mouse brain. Zyxin accumulates in the nucleus where it is co-localized with SIRT1 after treatment with leptomycin B in COS-7 cells. Furthermore, SIRT1 deacetylates zyxin, suggesting SIRT1 could interact with nuclear-accumulated zyxin and modulate its function through deacetylation.
  
  
  CONCLUSIONS
  Zyxin could be a novel interacting partner of SIRT1. Zyxin is an adaptor protein at focal adhesion plaque, regulating cytoskeletal dynamics and signal transduction to convey signal from the ECM (extracellular matrix) to the nucleus. Our results raise the possibility that SIRT1 regulates signal transmission from ECM to the nucleus by modulating the functions of zyxin via deacetylation.
authors.affiliation: Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan. yuki-fujita@molneu.med.osaka-u.ac.jp
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hata
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Endo
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D060589:Zyxin
chemical_list: D003598:Cytoskeletal Proteins; D006023:Glycoproteins; C092842:ZYX protein, human; D060589:Zyxin; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins