title: The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor.
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.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Or
authors.initials: O
authors.lastname: Gozani
authors.forename: Philip
authors.initials: P
authors.lastname: Karuman
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.forename: Dmitri
authors.initials: D
authors.lastname: Ivanov
authors.forename: James
authors.initials: J
authors.lastname: Cha
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Lugovskoy
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Baird
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Field
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Lessnick
authors.forename: Jennifer
authors.initials: J
authors.lastname: Villasenor
authors.forename: Bharat
authors.initials: B
authors.lastname: Mehrotra
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Rao
authors.forename: Joan S
authors.initials: JS
authors.lastname: Brugge
authors.forename: Colin G
authors.initials: CG
authors.lastname: Ferguson
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.forename: David G
authors.initials: DG
authors.lastname: Myszka
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Cantley
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
authors.forename: Nullin
authors.initials: N
authors.lastname: Divecha
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
authors.forename: Junying
authors.initials: J
authors.lastname: Yuan
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D000595:Amino Acid Sequence / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D005057:Eukaryotic Cells / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D018398:Homeodomain Proteins; C444654:ING2 protein, human; D018129:Phosphatidylinositol Phosphates; D018160:Receptors, Cytoplasmic and Nuclear; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C113567:phosphatidylinositol 5-phosphate; C040985:phosphatidylinositol receptors; D019870:1-Phosphatidylinositol 4-Kinase