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Cul3 neddylation is crucial for gradual lipid droplet formation during adipogenesis. | LitMetric

Cul3 neddylation is crucial for gradual lipid droplet formation during adipogenesis.

Biochim Biophys Acta Mol Cell Res

Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.

Published: August 2017

AI Article Synopsis

  • Cullin 3 (Cul3) is part of a family of proteins that helps regulate the ubiquitin-proteasome system, which tags and degrades proteins, and is crucial for fat cell development (adipogenesis).
  • During the differentiation of preadipocytes (LiSa-2 cells), Cul3 accumulates and its downregulation or blocking neddylation prevents the formation of lipid droplets (storage organelles for fats), indicating its role in fat storage.
  • The study shows a link between Cul3, Rab18 (a protein associated with lipid droplets), and RhoA (a suppressor of fat cell formation), where downregulation of Cul3 increases RhoA levels, suggesting Cul

Article Abstract

Cullin 3 (Cul3) belongs to the family of cullins (Cul1-7) providing the scaffold for cullin-RING ubiquitin (Ub) ligases (CRLs), which are activated by neddylation and represent essential E3 ligases of the Ub proteasome system. During adipogenic differentiation neddylated Cul3 accumulates in LiSa-2 preadipocytes. Downregulation of Cul3 and inhibition of neddylation by MLN4924 blocks the formation of lipid droplets (LDs), the lipid storage organelles and markers of adipogenesis. Neddylation of Cul3 coincides with an increase of Rab18, a GTPase associated with LDs. Immunoprecipitation and confocal fluorescence microscopy revealed physical association of Cul3 and Rab18 at the membrane of LDs. RhoA, a suppressor of adipogenesis decreased during differentiation. Our results in LiSa-2 cells, but also mouse embryonic fibroblasts revealed a connection between Cul3, Rab18 and RhoA. Downregulation of Cul3 led to a marked increase in RhoA protein expression after 6days of LiSa-2 cell differentiation, suggesting that Cul3 is involved in the regulation of RhoA stability.

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Source
http://dx.doi.org/10.1016/j.bbamcr.2017.05.009DOI Listing

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