The WD-repeat protein GRWD1: Potential roles in myeloid differentiation and ribosome biogenesis

A cDNA fragment originally identified in U-937 cells as a vitamin D-3-regulated gene is here designated the glulamate-rich WD-repeat (GRWD1) gene. WD-repeat proteins are a class of functionally divergent molecules that cooperate with other proteins to regulate cellular processes. GRWD1 encodes a 446-amino-acid protein containing a glutamate-rich region followed by four WD repeals, The yeast homologue of GRWD1, Rrb1, has been shown to be an essential protein involved in ribosome biogenesis. Northern analysis of GRWD1 message levels in the myeloid cell line HL-60 undergoing differentiation induced by vitamin D-3 Or retinoic acid demonstrate downregulation coincident with slowing of cellular proliferation. A siRNA designed to downregulate GRWD1 similarly results ill a decrease in Cellular proliferation within 293 cells. Metabolic labeling of cells expressing the siRNA to GRWD1 shows a decrease in global protein synthesis. Finally. nuclear fractionation studies show cosedimentation of GRWD1 with preribosomal complexes. as well as the WD-repeat-containing protein Bop1. which has previously been implicated in ribosome biogenesis. These studies suggest within within mammalian cells plays role in ribosome biogenesis and during inyeloid differentiation its levels are regulated. Published by Elsevier Inc.