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

Overview

MeSH Major

  • Endothelial Growth Factors
  • Fibroblasts
  • Genetic Vectors
  • Implants, Experimental
  • Lymphokines
  • Proto-Oncogene Proteins c-sis
  • Retroviridae
  • Skin
  • Transduction, Genetic
  • Wound Healing
  • Wounds and Injuries

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.

publication date

  • July 11, 2003

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/S0092-8674(03)00480-X

Additional Document Info

start page

  • 99

end page

  • 111

volume

  • 114

number

  • 1