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 Wagner; Nullin Divecha; Glenn D. Prestwich; Junying Yuan

doi:10.1016/S0092-8674(03)00480-X

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

Cancer Research UK Manchester Institute

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	99-111
Number of pages	12
Journal	Cell
Volume	114
Issue number	1
DOIs	https://doi.org/10.1016/S0092-8674(03)00480-X
Publication status	Published - 11 Jul 2003

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0092-8674(03)00480-X

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Gozani, O., Karuman, P., Jones, D. R., Ivanov, D., Cha, J., Lugovskoy, A. A., Baird, C. L., Zhu, H., Field, S. J., Lessnick, S. L., Villasenor, J., Mehrotra, B., Chen, J., Rao, V. R., Brugge, J. S., Ferguson, C. G., Payrastre, B., Myszka, D. G., Cantley, L. C., ... Yuan, J. (2003). The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor. Cell, 114(1), 99-111. https://doi.org/10.1016/S0092-8674(03)00480-X

@article{43d74dfa691d4d44b1652d22c6a9f152,

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.",

keywords = "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",

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

year = "2003",

month = jul,

day = "11",

doi = "10.1016/S0092-8674(03)00480-X",

language = "English",

volume = "114",

pages = "99--111",

journal = "Cell",

issn = "1097-4172",

publisher = "Cell Press",

number = "1",

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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 & Yuan, J 2003, 'The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor', Cell, vol. 114, no. 1, pp. 99-111. https://doi.org/10.1016/S0092-8674(03)00480-X

TY - JOUR

T1 - The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor

AU - Gozani, Or

AU - Karuman, Philip

AU - Jones, David R.

AU - Ivanov, Dmitri

AU - Cha, James

AU - Lugovskoy, Alexey A.

AU - Baird, Cheryl L.

AU - Zhu, Hong

AU - Field, Seth J.

AU - Lessnick, Stephen L.

AU - Villasenor, Jennifer

AU - Mehrotra, Bharat

AU - Chen, Jian

AU - Rao, Vikram R.

AU - Brugge, Joan S.

AU - Ferguson, Colin G.

AU - Payrastre, Bernard

AU - Myszka, David G.

AU - Cantley, Lewis C.

AU - Wagner, Gerhard

AU - Divecha, Nullin

AU - Prestwich, Glenn D.

AU - Yuan, Junying

PY - 2003/7/11

Y1 - 2003/7/11

N2 - 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.

AB - 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.

KW - metabolism: 1-Phosphatidylinositol 4-Kinase

KW - genetics: Amino Acid Sequence

KW - genetics: Apoptosis

KW - genetics: Base Sequence

KW - genetics: Cell Membrane

KW - genetics: Cell Nucleus

KW - genetics: DNA Damage

KW - metabolism: Eukaryotic Cells

KW - Genes, Tumor Suppressor

KW - antagonists & inhibitors: Homeodomain Proteins

KW - Humans

KW - Molecular Sequence Data

KW - metabolism: Phosphatidylinositol Phosphates

KW - genetics: Protein Binding

KW - genetics: Protein Structure, Tertiary

KW - RNA Interference

KW - genetics: Receptors, Cytoplasmic and Nuclear

KW - genetics: Signal Transduction

KW - Tumor Cells, Cultured

KW - genetics: Tumor Suppressor Protein p53

KW - Tumor Suppressor Proteins

U2 - 10.1016/S0092-8674(03)00480-X

DO - 10.1016/S0092-8674(03)00480-X

M3 - Article

SN - 1097-4172

VL - 114

SP - 99

EP - 111

JO - Cell

JF - Cell

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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