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- W2171508492 abstract "SREBP1 (Sterol regulatory element binding protein 1), transcription factor that regulates hundreds of genes involved in lipid metabolism and adipocyte differentiation, is a direct partner of A-type lamins. We show that i) in vitro, the tail regions of prelamin A, lamin A and lamin C bind a polypeptide of SREBP1 and ii) within cells, interactions between wild-type A-type lamins and SREBP1 occur mainly at the nuclear periphery but also within the nucleoplasm. While A-type lamin R482W mutation is responsible for Dunnigan type familial partial lipodystrophy (FPLD2), we show that both overexpression of LMNA p.R482W in primary human preadipocytes and endogenous expression of A-type lamins p.R482W in FPLD2 patient fibroblasts, reduce A-type lamins-SREBP1 in situ interactions and upregulates a large number of SREBP1 target genes[1]. As this LMNA mutant was previously shown to inhibit adipogenic differentiation, we propose that deregulation of SREBP1 by mutated A-type lamins constitutes one underlying mechanism of the physiopathology of FPLD2." @default.
- W2171508492 created "2016-06-24" @default.
- W2171508492 creator A5034163352 @default.
- W2171508492 date "2015-11-11" @default.
- W2171508492 modified "2023-09-30" @default.
- W2171508492 title "LMNA p.R482W mutation related to FPLD2 alters SREBP1-A type lamin interactions in human fibroblasts and adipose stem cells" @default.
- W2171508492 cites W2096154082 @default.
- W2171508492 doi "https://doi.org/10.1186/1750-1172-10-s2-o13" @default.
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