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

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Tsai RY,McKay RD

doi

10.1101/gad.55671

subject

Has Abstract

pub_date

2002-12-01 00:00:00

pages

2991-3003

issue

23

eissn

0890-9369

issn

1549-5477

journal_volume

16

pub_type

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