New frontiers in nucleolar research: Nucleostemin and related proteins

Abstract

Nucleostemin, guanine nucleotide binding protein-like 3-like (GNL3L), and Ngp-1 (also known as GNL-2) constitute a novel family of nucleolar GTP-binding proteins that are uniquely defined by the combination of five circularly permuted GTP-binding (G) motifs and nucleolar localization. These proteins elegantly reveal the versatility of the nucleolus. The most well-known member of this family is nucleostemin, which was first identified as a neural stem cell-enriched gene product and has later become a focus of attention in multiple research areas, including cell cycle regulation, telomere maintenance, stem cell biology, tumorigenesis, and tissue regeneration. It has also been used to illustrate the molecular mechanism that controls the dynamic shuttling behavior of nucleolar proteins between the nucleolar and nucleoplasmic compartments. New reports have come out that describe not only the biological importance of nucleostemin in mammals but also the functions of its vertebrate paralog, GNL3L, and their common invertebrate ortholog, GNL3. Current data indicate that nucleostemin and GNL3L may have diverged at the inception of vertebrate evolution, and that nucleostemin may have adopted new biological roles while GNL3L inherited the evolutionarily conserved function of GNL3. In vertebrates, nucleostemin, GNL3L, and Ngp-1 display distinct expression profiles and biological activities. They cogently illustrate the complexity of nucleolar biology by showing how this classic organelle integrates a variety of extra- and intra-cellular signals to control key biological events in a dynamic and cell type-specific manner. © 2011 Springer Science+Business Media, LLC.