出版社：American Society for Biochemistry and Molecular Biology
摘要：The liver X receptor (LXR) is a member of the nuclear hormonereceptor superfamily that plays an important role in lipid homeostasis.Here we characterize two alternative human LXR transcripts,designated LXR2 and LXR3. All three LXR isoforms are derivedfrom the same gene via alternative splicing and differentialpromoter usage. The LXR2 isoform lacks the first 45 amino acidsof LXR1, and is generated through the use of a novel promoterand first exon. LXR3 lacks 50 amino acids within the ligandbinding domain and is generated through alternative recognitionof the 3'-splice site in exon 6. LXR2 and LXR3 are expressedat lower levels compared with LXR1 in most tissues, except thatLXR2 expression is dominant in testis. Both LXR2 and LXR3 heterodimerizewith the retinoid X receptor and bind to LXR response elements.LXR2 shows reduced transcriptional activity relative to LXR1,indicating that the N-terminal domain of LXR is essential forits full transcriptional activity. LXR3 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 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
(LXR
