1. The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor.
- Author
-
Gozani O, Karuman P, Jones DR, Ivanov D, Cha J, Lugovskoy AA, Baird CL, Zhu H, Field SJ, Lessnick SL, Villasenor J, Mehrotra B, Chen J, Rao VR, Brugge JS, Ferguson CG, Payrastre B, Myszka DG, Cantley LC, Wagner G, Divecha N, Prestwich GD, and Yuan J
- Subjects
- 1-Phosphatidylinositol 4-Kinase metabolism, Amino Acid Sequence genetics, Base Sequence genetics, Cell Membrane genetics, Cell Membrane metabolism, Cell Nucleus genetics, Genes, Tumor Suppressor, Homeodomain Proteins antagonists & inhibitors, Homeodomain Proteins genetics, Humans, Molecular Sequence Data, Phosphatidylinositol Phosphates metabolism, Protein Binding genetics, Protein Structure, Tertiary genetics, RNA Interference, Receptors, Cytoplasmic and Nuclear genetics, Tumor Cells, Cultured, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Apoptosis genetics, Cell Nucleus metabolism, DNA Damage genetics, Eukaryotic Cells metabolism, Homeodomain Proteins metabolism, Receptors, Cytoplasmic and Nuclear metabolism, Signal Transduction genetics, Tumor Suppressor Proteins
- Abstract
Phosphoinositides (PtdInsPs) play critical roles in cytoplasmic signal transduction pathways. However, their functions in the nucleus are unclear, as specific nuclear receptors for PtdInsPs have not been identified. Here, we show that ING2, a candidate tumor suppressor protein, is a nuclear PtdInsP receptor. ING2 contains a plant homeodomain (PHD) finger, a motif common to many chromatin-regulatory proteins. We find that the PHD fingers of ING2 and other diverse nuclear proteins bind in vitro to PtdInsPs, including the rare PtdInsP species, phosphatidylinositol 5-phosphate (PtdIns(5)P). Further, we demonstrate that the ING2 PHD finger interacts with PtdIns(5)P in vivo and provide evidence that this interaction regulates the ability of ING2 to activate p53 and p53-dependent apoptotic pathways. Together, our data identify the PHD finger as a phosphoinositide binding module and a nuclear PtdInsP receptor, and suggest that PHD-phosphoinositide interactions directly regulate nuclear responses to DNA damage.
- Published
- 2003
- Full Text
- View/download PDF