CAR Alternatively Spliced mRNAs

There have been extensive efforts to characterize and understand the functional consequences of alternatively spliced CAR isoforms. Approximately 26 alternatively spliced isoforms of CAR, originating from combinations of around eight splicing events, have been described for CAR (reviewed earlier [60]). In this section, we will discuss alternatively spliced isoforms of CAR that have been functionally characterized by various investigators. 

The most common and extensively investigated CAR isoforms are characterized by a 12 bp insertion at the 5 end of exon 7 (SV23) resulting in an in-frame insertion of four amino acids (SPTV) and a 15 bp insertion at the 5 end of exon 8 (SV24) resulting in an in-frame insertion of five amino acids (APYLT), respectively. These two events can occur independent of each other or together. 

SV23 characterized by a four amino acid insertion in the LBD adds an extra loop between helices 6 and 7. This isoform interacts weakly with CAR response elements and with various coactivators [61-65]. This variant was capable of transactivating CYP2B6 and MDR1 reporters in some studies but not CYP3A4 and IJGT1A1 reporters [61-65], Recently, it has been shown that upon RXRa overexpression SV23 shows RXR-dependent transactivation activity and interaction with SRC-1 as well as RXR-dependent response to clotrimazole and androstanol [66]. 

Use of alls rate Prematofe Eernunaton codon In farm in farm in frame 

Eflecl on Drolein Loss df firrt zinc finper Loss of CAR expression Extra loop 

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