Subcellular localization of SREBP1 depends on its interaction with the C-terminal region of wild-type and disease related A-type lamins
- Laboratoire du Stress et Pathologies du Cytosquelette, Universite Paris Diderot-Paris 7, CNRS, Institut de Biologie Fonctionnelle et Adaptative, 4 rue M.A. Lagroua Weill Halle, 75205 Paris cedex 13 (France)
- Laboratoire de Biologie Structurale et Radiobiologie, URA CNRS 2096, Commissariat a l'Energie Atomique Saclay, 91190 Gif-sur-Yvette (France)
- INSERM U759, Institut Curie/Universite de Paris-Sud, 91405 Orsay Cedex (France)
- Institut Jacques Monod, UMR 7592, Universite Paris Diderot-Paris 7, CNRS, 15 rue Helene Brion, 75205 Paris (France)
- Department of Medicine and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States)
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 ( Increment 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.
- OSTI ID:
- 22212253
- Journal Information:
- Experimental Cell Research, Vol. 317, Issue 20; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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