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Sci. Signal., 19 June 2012
Vol. 5, Issue 229, p. ra44
[DOI: 10.1126/scisignal.2003111]


Editor's Summary

Targeting the Lipid Ligand to Regulate Transcription
Steroidogenic factor 1 (SF-1) is a nuclear receptor that transcriptionally activates genes involved in sexual development and reproduction. Blind et al. found that phosphatidylinositol 4,5-bisphosphate (PIP2) bound to SF-1 was phosphorylated by inositol polyphosphate multikinase (IPMK) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). Conversely, the lipid phosphatase PTEN dephosphorylated the SF-1–PIP3 complex. The transcriptional activity of SF-1 was decreased in cells after inhibiting IPMK and increased in cells overexpressing PTEN. Thus, phosphorylation of its associated lipid, rather than the nuclear receptor itself, activates SF-1 and identifies another signaling role for nuclear phosphoinositides.

Citation: R. D. Blind, M. Suzawa, H. A. Ingraham, Direct Modification and Activation of a Nuclear Receptor–PIP2 Complex by the Inositol Lipid Kinase IPMK. Sci. Signal. 5, ra44 (2012).

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