A circularly permuted subfamily of the Ras GTPases
Nucleostemin (NS) is a nucleolar protein that functions as a regulator of cell growth and proliferation in stem cells and in several types of cancer cells, but is not expressed in the differentiated cells of most mammalian adult tissues. NS shuttles between the nucleolus and nucleoplasm bidirectionally at a rate that is fast and independent of cell type. Lowering GTP levels decreases the nucleolar retention of NS, and expression of NS is abruptly down-regulated during differentiation prior to terminal cell division. Found only in eukaryotes, NS consists of an N-terminal basic domain, a coiled-coil domain, a GTP-binding domain, an intermediate domain, and a C-terminal acidic domain. Experimental evidence indicates that NS uses its GTP-binding property as a molecular switch to control the transition between the nucleolus and nucleoplasm, and this process involves interaction between the basic, GTP-binding, and intermediate domains of the protein.