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Sci. STKE, 29 June 2004
Vol. 2004, Issue 239, p. tw232
[DOI: 10.1126/stke.2392004TW232]


CELL GROWTH Insulin Controls Ribosome Synthesis

A eukaryotic cell must double its size before cell division, and this growth is regulated in part by ribosome biogenesis. RNA polymerase I directs the synthesis of rRNA through interactions with other nuclear proteins, including upstream binding factor 1 (UBF1). Interaction of UBF1 with insulin receptor substrate 1 (IRS-1), an adaptor protein for the insulin and insulin-like growth factor 1 (IGF-1) receptors, suggested a mechanism by which insulin could regulate cell size. IRS protein has been observed in the nucleus, and lack of IRS protein or its downstream effectors reduces cell size in the fly and mouse. Drakas et al. report that IRS-1 binds to its downstream effector, phosphatidylinositol 3-kinase (PI3K), in nuclear lysates of mouse fibroblasts that were treated with IGF-1. PI3K also interacted with UBF1 in these nuclear lysates, which suggests a nuclear tricomplex between IRS-1, PI3K, and UBF. In the absence of IRS-1, UBF1 was not serine-phosphorylated (and thus, not activated) in response to IGF-1. Expression of IRS-1 increased UBF phosphorylation in response to IGF-I treatment. Immunoprecipitated UBF1 was also phosphorylated by purified PI3K in vitro, which suggests that UBF1 is a direct substrate. Because UBF1 can be phosphorylated by other kinases, the authors propose that an IRS-1 to PI3K to UBF1 pathway may not be the only mechanism controlling UBF1-dependent regulation of cell size.

R. Drakas, Z. Tu, R. Baserga, Control of cell size through phosphorylation of upstream binding factor 1 by nuclear phosphatidylinositol 3-kinase. Proc. Natl. Acad. Sci. U.S.A. 101, 9272-9276 (2004). [Abstract] [Full Text]

Citation: Insulin Controls Ribosome Synthesis. Sci. STKE 2004, tw232 (2004).

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