Isolation and characterization of human and mouse WDR19,a novel WD-repeat protein exhibiting androgen-regulated expression in prostate epithelium.

ABSTRACT

Androgens regulate important processes involved in the normal development and function of the human and rodent prostate glands. Here we report the isolation and characterization of a new androgen-regulated gene, designated WDR19, that encodes repeating sequence motifs found in the WD-repeat family of proteins. The WD repeat is a conserved domain of approximately 40 amino acids that is typically bracketed by glycine-histidine and tryptophan-aspartic acid (WD) dipeptides. WD-repeat proteins are a large group of structurally related proteins that participate in a wide range of cellular functions, including transmembrane signaling, mRNA modification, vesicle formation, and vesicular trafficking. The WDR19 gene comprises 36 exons and is located on chromosome 4p15-4p11. The predicted protein contains six WD repeats, a clathrin heavy-chain repeat, and three transmembrane domains. Sequence analysis reveals that the WDR19 gene is conserved from Caenorhabditis elegans to human. WDR19 is expressed in normal and neoplastic prostate epithelium as demonstrated by RNA in situ hybridization and is regulated by androgenic hormones. WDR19 transcripts exhibit alternative splicing in which two isoforms appear to be prostate restricted, a property that could be exploited for designing diagnostic or therapeutic strategies for prostate carcinoma.