Fad24, a mammalian homolog of Noc3p, is a positive regulator in adipocyte differentiation

Abstract

Adipocyte differentiation is controlled by complex actions involving gene expression and signal transduction. From metaphase to anaphase, peroxisome proliferator-activated receptor gamma, the CCAAT/enhancer-binding protein family and sterol regulatory element-binding protein-1 are known to function as master regulators. However, the mechanism underlying the earliest step, which triggers the initiation of differentiation, remains unknown. In previous reports, we have isolated a number of genes, whose expression increases in the early stage of differentiation in the mouse 3T3-L1 preadipocyte cell line. Here we report the cloning of the full-length cDNA and characterization of an unknown gene isolated previously and named fad24 (factor for adipocyte differentiation 24). Fad24 encodes a protein consisting of 807 amino acids. The deduced amino acid sequence was shown to have a basic leucine zipper motif and a NOC domain. Expression of fad24 was rapidly induced after stimulation with inducers. Furthermore, overexpression of fad24 in NIH-3T3 cells promoted adipogenesis in the presence of a ligand for peroxisome proliferator-activated receptor gamma. FAD24 localizes in the nucleus, especially within nuclear speckles. As the nuclear speckle functions as a nascent transcription and pre-mRNA splicing machinery, there is a possibility that FAD24 functions as one of the components for transcription and/or pre-mRNA splicing and positively regulates adipocyte differentiation.