Liver X receptor beta with mutations in the activation function-2 region is excluded from the nucleolus.
Liver X receptors (LXRs) alpha and beta are ligand-induced transcription factors that regulate transcription of genes encoding key regulators of cholesterol metabolism and transport, and of lipogenesis. Despite their high similarity, LXRalpha is the functionally dominant LXR isotype in the liver. The function of nuclear proteins can be affected by their sequestration in the nucleoli. Whereas most nuclear receptors are excluded from the nucleolus, some are not. To explore nucleolar exclusion of LXRalpha and LXRbeta, we used cells expressing cyan fluorescent protein (CFP) chimeras with LXRalpha (CFP-LXRalpha) and wild-type and mutant CFP-LXRbeta and marked the nucleolus with anti-fibrillarin antibody. Significantly more CFP-LXRbeta than CFP-LXRalpha in the nucleoli. Mutations in basic-rich sequences in the DNA binding domain caused some exclusion of CFP-LXRbeta from the nucleolus. Moreover, mutations in the activation function-2, an important protein-protein interaction site in all nuclear receptors, resulted in exclusion of CFP-LXRbeta from the nucleolus. These data suggest protein-protein interactions that may regulate nucleolar sequestration of LXRbeta.
Department of Biological Sciences, Louisiana State University, Baton Rouge, 70803, United States.
Rajuli
R
Lall
Sarah
S
Kuruvilla
Kirsten
K
Prüfer
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000378:metabolism; D000071518:Liver X Receptors; D008969:Molecular Sequence Data; D009154:Mutation; D057093:Orphan Nuclear Receptors; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D016335:Zinc Fingers / Q000235:genetics
C485182:Cyan Fluorescent Protein; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins