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Publication : A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells.

First Author  Tsai RY Year  2002
Journal  Genes Dev Volume  16
Issue  23 Pages  2991-3003
PubMed ID  12464630 Mgi Jnum  J:80512
Mgi Id  MGI:2445992 Doi  10.1101/gad.55671
Citation  Tsai RY, et al. (2002) A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Genes Dev 16(23):2991-3003
abstractText  The unique property of stem cells to self-renew suggests specific mechanisms that regulate their cell-cycle progression. In the present study, we identify a novel protein, nucleostemin, found in the nucleoli of CNS stem cells, embryonic stem cells, and several cancer cell lines and preferentially expressed by other stem cell-enriched populations. It contains an N-terminal basic domain and two GTP-binding motifs. When stem cells differentiate, nucleostemin expression decreases rapidly prior to cell-cycle exit both in vitro and in vivo. Depletion or overexpression of nucleostemin reduces cell proliferation in CNS stem cells and transformed cells. Mutation analysis indicates that excessive nucleostemin, particularly mutants that lack the GTP-regulatory domain, prevents cells from entering mitosis and causes apoptosis in a p53-dependent manner. The N-terminal basic domain specifies nucleolar localization, the p53 interaction, and is required for the cell death caused by overexpression. This work describes a novel nucleolar mechanism that controls the cell-cycle progression in CNS stem cells and cancer cells.
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