A multistep, GTP-driven mechanism controlling the dynamic cycling of nucleostemin.
Nucleostemin (NS) was identified as a stem cell- and cancer cell-enriched nucleolar protein that controls the proliferation of these cells. Here, we report the mechanism that regulates its dynamic shuttling between the nucleolus and nucleoplasm. The nucleolar residence of nucleostemin involves a transient and a long-term binding by the basic and GTP-binding domains, and a dissociation mechanism mediated by the COOH-terminal region. This cycle is propelled by the GTP binding state of nucleostemin. We propose that a rapid nucleostemin cycle is designed to translate extra- and intra-cellular signals into the amount of nucleostemin in the nucleolus in a bidirectional and fast manner.
Tsai
Robert Y L
RY
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. rtsai@ibt.tamhsc.edu
McKay
Ronald D G
RD
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D003609:Dactinomycin / Q000494:pharmacology; D036681:Fluorescence Recovery After Photobleaching; D019204:GTP-Binding Proteins; D049452:Green Fluorescent Proteins / Q000235:genetics; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D042581:Intranuclear Space / Q000378:metabolism; D007700:Kinetics; D018613:Microscopy, Confocal; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009173:Mycophenolic Acid / Q000494:pharmacology; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*
D002352:Carrier Proteins; C469949:GNL3 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D049452:Green Fluorescent Proteins; D003609:Dactinomycin; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D009173:Mycophenolic Acid