The low density lipoprotein receptor in Xenopus laevis. II. Feedback repression mediated by conserved sterol regulatory element

Abstract

The 5'-flanking regions of the two low density lipoprotein (LDL) receptor genes in Xenopus laevis contain three repeat sequences that are virtually identical to the repeats that mediate sterol-regulated transcription of the human LDL receptor gene. Like their human counterparts, Xenopus repeats 1 and 3, but not repeat 2, bind the transcription factor Sp1 and thus probably function as positive transcription elements. Xenopus repeat 2, like human repeat 2, contains all of the nucleotides that are required for sterol regulation. Administration of sterols repressed Xenopus LDL receptor mRNA in cultured A6 kidney cells and in the liver of intact frogs. In frogs this repression was associated with a 2-fold increase in plasma LDL levels. Xenopus LDL contains a protein corresponding in size to human apoB-100, a ligand for the LDL receptor. We found no evidence that frog plasma contains B-48, nor did we observe a clear-cut protein corresponding to apoE. We conclude that the structural gene for the LDL receptor has been under sterol-mediated regulation at least since the time of amphibian development more than 350 million years ago.