Subcellular localization of SREBP1 depends on its interaction with the C-terminal region of wild-type and disease related A-type lamins.
Exp Cell Res
; 317(20): 2800-13, 2011 Dec 10.
Article
in En
| MEDLINE
| ID: mdl-21993218
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lamin Type A
/
Sterol Regulatory Element Binding Protein 1
Limits:
Humans
Language:
En
Journal:
Exp Cell Res
Year:
2011
Document type:
Article
Affiliation country:
France