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A multistep, GTP-driven mechanism controlling the dynamic cycling of nucleostemin
Robert Y.L. Tsai1,2, and
Ronald D.G. McKay1
1 Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 2 Center for Cancer Biology and Nutrition, Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030
Correspondence to R.Y.L. Tsai: rtsai{at}ibt.tamhsc.edu
Abstract:
Nucleostemin (NS) was identified as a stem cell and cancercellenriched nucleolar protein that controls the proliferationof these cells. Here, we report the mechanism that regulatesits dynamic shuttling between the nucleolus and nucleoplasm.The nucleolar residence of nucleostemin involves a transientand 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 translateextra- and intra-cellular signals into the amount of nucleosteminin the nucleolus in a bidirectional and fast manner.
Abbreviations used in this paper: Act-D, actinomycin D; iFRAP,inverse FRAP; MPA, mycophenolic acid; NS, nucleostemin.
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