Allosteric regulation of even-skipped repression activity by phosphorylation.

The Drosophila homeodomain protein Even-skipped (Eve) is a well characterized transcriptional repressor. Here, we show that Eve's ability to function in vitro is negatively regulated by phosphorylation. DNA-binding activity was unaffected by phosphorylation, but phosphorylated Eve was unable to interact with the TATA-binding protein (TBP), a known target for repression. Unexpectedly, phosphorylation of the Eve N terminus, which is dispensable for repression and TBP binding, was necessary and sufficient to inactivate Eve. LiCl, which specifically inhibits glycogen synthase kinase-3 (GSK-3), reduced Eve phosphorylation in nuclear extract and blocked inhibition of repression. In addition, Eve was phosphorylated and inactivated by purified GSK-3 beta plus casein kinase II. Our results suggest a novel mechanism of transcriptional control involving phosphorylation-induced allosteric interference with a repressive protein-protein interaction.

• Publication year

  1999

• Venue

  Molecules and Cells

• Publication date

  Unknown publication date

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/S1097-2765(00)80176-8PMID 10024881
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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