The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor

Or Gozani, Philip Karuman, David R. Jones, Dmitri Ivanov, James Cha, Alexey A. Lugovskoy, Cheryl L. Baird, Hong Zhu, Seth J. Field, Stephen L. Lessnick, Jennifer Villasenor, Bharat Mehrotra, Jian Chen, Vikram R. Rao, Joan S. Brugge, Colin G. Ferguson, Bernard Payrastre, David G. Myszka, Lewis C. Cantley, Gerhard WagnerNullin Divecha, Glenn D. Prestwich, Junying Yuan

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)99-111
Number of pages12
Issue number1
Publication statusPublished - 11 Jul 2003


  • metabolism: 1-Phosphatidylinositol 4-Kinase
  • genetics: Amino Acid Sequence
  • genetics: Apoptosis
  • genetics: Base Sequence
  • genetics: Cell Membrane
  • genetics: Cell Nucleus
  • genetics: DNA Damage
  • metabolism: Eukaryotic Cells
  • Genes, Tumor Suppressor
  • antagonists & inhibitors: Homeodomain Proteins
  • Humans
  • Molecular Sequence Data
  • metabolism: Phosphatidylinositol Phosphates
  • genetics: Protein Binding
  • genetics: Protein Structure, Tertiary
  • RNA Interference
  • genetics: Receptors, Cytoplasmic and Nuclear
  • genetics: Signal Transduction
  • Tumor Cells, Cultured
  • genetics: Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins


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