The PHD Finger of the Chromatin-Associated Protein ING2 Functions as a Nuclear Phosphoinositide Receptor
| Autor: | Gerhard Wagner, Philip Karuman, David R. Jones, Bernard Payrastre, David G. Myszka, Joan S. Brugge, Nullin Divecha, Jian Chen, Colin G. Ferguson, Or Gozani, Cheryl L. Baird, Glenn D. Prestwich, Bharat Mehrotra, Jennifer Villasenor, Dmitri N. Ivanov, Junying Yuan, Alexey Lugovskoy, Seth J. Field, James Cha, Hong Zhu, Stephen L. Lessnick, Vikram R. Rao, Lewis C. Cantley |
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| Rok vydání: | 2003 |
| Předmět: |
education
Molecular Sequence Data Receptors Cytoplasmic and Nuclear Apoptosis Biology General Biochemistry Genetics and Molecular Biology Candidate Tumor Suppressor Protein Phosphatidylinositol Phosphates Tumor Cells Cultured Humans Genes Tumor Suppressor Amino Acid Sequence Nuclear protein Receptor Phosphatidylinositol 5-phosphate 1-Phosphatidylinositol 4-Kinase Genetics Cell Nucleus Homeodomain Proteins Base Sequence Biochemistry Genetics and Molecular Biology(all) Tumor Suppressor Proteins Cell Membrane Chromatin Cell biology Protein Structure Tertiary Eukaryotic Cells Nuclear receptor PHD finger RNA Interference Signal transduction Tumor Suppressor Protein p53 DNA Damage Protein Binding Signal Transduction |
| Zdroj: | Cell. 114(1):99-111 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/s0092-8674(03)00480-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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