TISSUE-SPECIFIC REGULATION BY VITAMIN-D-3 OF A NOVEL PROTEIN CONTAINING ANKYRIN-LIKE REPEATS

Vitamin D-3 is the precursor of the steroid hormone 1,25-dihydroxyvita min D-3 which is involved in the regulation of calcium metabolism, gro wth and differentiation. We used differential display of mRNA populati ons from kidney and intestine of vitamin D-3-deficient and -replete ch icks to determine the steady-state abundance of approximately 5000 mRN As. One of these sequences, whose differential expression in kidney an d down-regulation by vitamin D-3 was confirmed by Northern analysis, w as used to screen a cDNA library from vitamin D-3-deficient chick kidn ey in order to obtain a full-length cDNA. Subcloning and sequencing re vealed that this cDNA encodes a novel protein containing ankyrin-like repeats and a C-terminal Fe-S binding region signature. The encoded pr otein consists of 617 amino acids and contains two sets of four ankyri n-like repeats separated by 146 amino acids. This motif consists of ap proximately 33 amino acids containing a highly conserved central hydro phobic alpha helix and is abundant in a wide variety of proteins, part icularly those participating in the protein-protein or protein-membran e interactions involved in signal transduction, regulation of the cell cycle and control of transcription. Outside of the ankyrin-like domai ns, no homologies with other proteins in existing data bases were foun d. Our results have revealed a novel protein containing ankyrin-like r epeats tissue-specifically down-regulated by vitamin D-3 in the kidney . Copyright (C) 1997 Elsevier Science Ireland Ltd.