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Exp Cell Res. 2008 Aug 15;314(14):2652-60. doi: 10.1016/j.yexcr.2008.05.005. Epub 2008 May 27.

Mutations in the AF-2 region abolish ligand-induced intranuclear immobilization of the liver X receptor alpha.

Author information

  • 1Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. kprufer@lsu.edu

Abstract

The liver X receptors (LXR) alpha and beta are ligand-induced transcription factors that regulate the expression of genes important for cholesterol metabolism, lipogenesis, and other metabolic pathways. Despite their high degree of similarity, LXRs have redundant as well as nonredundant functions. The regulation of LXRs' intranuclear mobility most likely plays a major role in the regulation of their transcriptional activities. In order to elucidate how ligand binding, receptor-protein and receptor-DNA interactions affect intranuclear receptor mobility, we expressed transcriptionally active yellow fluorescent protein (YFP)-LXR alpha and YFP-LXR beta in Cos-7 cells. We used the fluorescence recovery after photobleaching (FRAP) technique and confocal laser scanning microscopy as well as Triton X-100 permeabilization experiments and fluorescence microscopy to measure differences in the intranuclear mobility between LXR alpha and LXR beta. The image analyses revealed that after agonist binding, LXR alpha exhibits slower intranuclear trafficking and greater intranuclear immobilization compared with LXR beta. In addition, mutational analysis showed that the integrity of the Activation Function (AF)-2 region of LXR alpha is essential for its immobilization whereas the integrity of the DNA binding domain is not. These findings imply that specific protein interactions with the AF-2 region of LXR alpha play a role in its intranuclear immobilization.

PMID:
18599038
[PubMed - indexed for MEDLINE]
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