期刊
BIOCHEMICAL JOURNAL
卷 411, 期 -, 页码 227-231出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20080134
关键词
cytokine; embryonic stem cell; homeodomain; Nanog; pluripotency rheostat; self-renewal
资金
- Medical Research Council [G0700711B, G19/38] Funding Source: researchfish
- Medical Research Council [G19/38] Funding Source: Medline
The defining activity of the homeodomain protein Nanog is the ability to confer cytokine-independent self-renewal upon ES (embryonic stem) cells in which it is overexpressed. However, the biochemical basis by which Nanog achieves this function remains unknown. In the present study, we show that Nanog dimerizes through a functionally critical domain. Co-immunoprecipitation of Nanog molecules tagged with distinct epitopes demonstrates that Nanog self-associates through a region in which every fifth residue is tryptophan. In vitro binding experiments establish that this region participates directly in self-association. Moreover, analytical ultracentrifugation indicates that, in solution, Nanog is in equilibrium between monomeric and dimeric forms with a K-d of 3 mu M. The functional importance of Nanog dimerization is established by ES cell colony-forming assays in which deletion of the tryptophan-repeat region eliminates the capacity of Nanog to direct LIF (leukaemia inhibitory factor)-independent self-renewal.
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