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| Titre : |
SREBP1 function depends on a-type lamin expression levels (poster) |
| Type de document : |
Article |
| Auteurs : |
Attanda W ; Duband-Goulet I ; Vadrot N ; Cabet E ; Ostlund C ; Worman H ; Zinn-Justin S |
| Congrès : |
4th International Congress of Myology, 4ème colloque international de Myologie (9-13 mai 2011; Lille (France)) |
| Editeur : |
AFM-TELETHON |
| Année de publication : |
2011 |
| Pages : |
p. 71 |
| Langues : |
Anglais (eng) |
| Mots-clés : | colloque
| | Résumé : | Prelamin A and mature lamin A are A-type lamins, nuclear intermediate filament proteins that play a role in organizing the chromatin structure and gene expression. Lamin A results from the proteolytic processing of prelamin A. It is shorter (646 aa instead of 664) and unfarnesylated, due to the cleavage of its c-terminal end by the enzyme Zmpste (Young et al. 2006). The sterol regulatory element binding protein 1 (SREBP1), a member of the basic-helix-loop-helix (bHLH)-leucine zipper family of transcription factors, has been reported to bind to lamin A. After binding to its specific DNA sequences (E-Box and SRE sequences), SREBP1 dimers induce the expression of target genes involved in adipogenesis and membrane biogenesis (Nohturfft et al., 2009). A SREBP1 polypeptide (aa 227-487) interacts with the c-terminal region of prelamin A (aa 389-664) in vitro (Lloyd et al. 2002). In cells from patients with lamin A/C gene mutations causing lipodystrophy, prelamin A accumulates because of inefficient processing and associates with SREBP1 (Capanni et al. 2005).Here we asked whether high levels of prelamin A would directly impact SREBP1 function. We therefore designed a gene reporter assay, based on SREBP1-mediated activation of a promoter containing sterol regulatory elements (SREs) driving the expression of a Firefly luciferase gene. The transcriptional activity of SREBP1 was determined in HeLa cells co-expressing ectopic SREBP1 and prelamin A. We compared the impact of the wild-type prelamin A, which is processed into mature lamin A to that of the mutant variant L647R which can not be processed. Our data show that the transcriptional activity of HA-SREBP1 is significantly reduced when it is co-expressed with either wild-type or mutant ectopic prelamin A. In addition, we observed that i) the subnuclear distribution of the lamin-binding SREBP1 polypeptide (aa 227-487) varies upon prelamin A overexpression and that ii) this SREBP1 polypeptide co-immunoprecipitates with both ectopic prelamin A and lamin A.Our data support a model in which the negative impact of A-type lamins on the function of SREBP1 is a consequence of the interaction between these two proteins. They further suggest that the expression level of A-type lamins is critical for the regulation of SREBP1 function. |
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