title: Subcellular localization of SREBP1 depends on its interaction with the C-terminal region of wild-type and disease related A-type lamins.
abstract: Lamins A and C are nuclear intermediate filament proteins expressed in most differentiated somatic cells. Previous data suggested that prelamin A, the lamin A precursor, accumulates in some lipodystrophy syndromes caused by mutations in the lamin A/C gene, and binds and inactivates the sterol regulatory element binding protein 1 (SREBP1). Here we show that, in vitro, the tail regions of prelamin A, lamin A and lamin C bind a polypeptide of SREBP1. Such interactions also occur in HeLa cells, since expression of lamin tail regions impedes nucleolar accumulation of the SREBP1 polypeptide fused to a nucleolar localization signal sequence. In addition, the tail regions of A-type lamin variants that occur in Dunnigan-type familial partial lipodystrophy of (R482W) and Hutchison Gilford progeria syndrome (∆607-656) bind to the SREBP1 polypeptide in vitro, and the corresponding FLAG-tagged full-length lamin variants co-immunoprecipitate the SREBP1 polypeptide in cells. Overexpression of wild-type A-type lamins and variants favors SREBP1 polypeptide localization at the intranuclear periphery, suggesting its sequestration. Our data support the hypothesis that variation of A-type lamin protein level and spatial organization, in particular due to disease-linked mutations, influences the sequestration of SREBP1 at the nuclear envelope and thus contributes to the regulation of SREBP1 function.
authors: Laboratoire du Stress et Pathologies du Cytosquelette, Université Paris Diderot-Paris 7, CNRS, Institut de Biologie Fonctionnelle et Adaptative, 4 rue M.A. Lagroua Weill Halle, 75205 Paris cedex 13, France.
authors: Isabelle
authors: I
authors: Duband-Goulet
authors: Stephanie
authors: S
authors: Woerner
authors: Sylvaine
authors: S
authors: Gasparini
authors: Wikayatou
authors: W
authors: Attanda
authors: Emilie
authors: E
authors: Kondé
authors: Carine
authors: C
authors: Tellier-Lebègue
authors: Constantin T
authors: CT
authors: Craescu
authors: Aurélie
authors: A
authors: Gombault
authors: Pascal
authors: P
authors: Roussel
authors: Nathalie
authors: N
authors: Vadrot
authors: Patrick
authors: P
authors: Vicart
authors: Cecilia
authors: C
authors: Ostlund
authors: Howard J
authors: HJ
authors: Worman
authors: Sophie
authors: S
authors: Zinn-Justin
authors: Brigitte
authors: B
authors: Buendia
mesh_terms: D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D052496:Lipodystrophy, Familial Partial / Q000235:genetics / Q000378:metabolism; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011371:Progeria / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
chemical_list: D034904:Lamin Type A; D009687:Nuclear Proteins; D010455:Peptides; D011498:Protein Precursors; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; C440308:lamin C; C090764:prelamin A