文章基本信息

标题：Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha
本地全文：下载
作者：Chen, Mingyi ; Beaven, Simon ; Tontonoz, Peter 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2005
卷号：46
期号：12
页码：2570-2579
DOI：10.1194/jlr.M500157-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：The liver X receptor ${alpha}$ (LXR ${alpha}$ ) is a member of the nuclear hormonereceptor superfamily that plays an important role in lipid homeostasis.Here we characterize two alternative human LXR ${alpha}$ transcripts,designated LXR ${alpha}$ 2 and LXR ${alpha}$ 3. All three LXR ${alpha}$ isoforms are derivedfrom the same gene via alternative splicing and differentialpromoter usage. The LXR ${alpha}$ 2 isoform lacks the first 45 amino acidsof LXR ${alpha}$ 1, and is generated through the use of a novel promoterand first exon. LXR ${alpha}$ 3 lacks 50 amino acids within the ligandbinding domain and is generated through alternative recognitionof the 3'-splice site in exon 6. LXR ${alpha}$ 2 and LXR ${alpha}$ 3 are expressedat lower levels compared with LXR ${alpha}$ 1 in most tissues, except thatLXR ${alpha}$ 2 expression is dominant in testis. Both LXR ${alpha}$ 2 and LXR ${alpha}$ 3 heterodimerizewith the retinoid X receptor and bind to LXR response elements.LXR ${alpha}$ 2 shows reduced transcriptional activity relative to LXR ${alpha}$ 1,indicating that the N-terminal domain of LXR ${alpha}$ is essential forits full transcriptional activity. LXR ${alpha}$ 3 is unable to bind ligandand is transcriptionally inactive. These observations outline a previously unrecognized role forthe N terminus in LXR function and suggest that the expressionof alternative LXR ${alpha}$ transcripts in certain biological contextsmay impact LXR signaling and lipid metabolism. Abbreviations: AF, activation function; DBD, DNA binding domain; LBD, ligand binding domain; LXR, liver X receptor; LXRE, LXR response element; RXR, retinoid X receptor Supplementary key words nuclear receptor • cholesterol metabolism • transcriptional regulation • RXR