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Published 18 January 2005. doi:10.1083/jcb.200409053
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 2, 179-184
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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 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.

Abbreviations used in this paper: Act-D, actinomycin D; iFRAP, inverse FRAP; MPA, mycophenolic acid; NS, nucleostemin.


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