Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors

Ian G Mills, Luke Gaughan, Craig Robson, Theodora Ross, Stuart McCracken, John Kelly, David E Neal

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

Internalization of activated receptors regulates signaling, and endocytic adaptor proteins are well-characterized in clathrin-mediated uptake. One of these adaptor proteins, huntingtin interacting protein 1 (HIP1), induces cellular transformation and is overexpressed in some prostate cancers. We have discovered that HIP1 associates with the androgen receptor through a central coiled coil domain and is recruited to DNA response elements upon androgen stimulation. HIP1 is a novel androgen receptor regulator, significantly repressing transcription when knocked down using a silencing RNA approach and activating transcription when overexpressed. We have also identified a functional nuclear localization signal at the COOH terminus of HIP1, which contributes to the nuclear translocation of the protein. In conclusion, we have discovered that HIP1 is a nucleocytoplasmic protein capable of associating with membranes and DNA response elements and regulating transcription.

Original languageEnglish
Pages (from-to)191-200
Number of pages10
JournalThe Journal of cell biology
Volume170
Issue number2
DOIs
Publication statusPublished - 18 Jul 2005

Keywords

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Cell Membrane
  • Cell Nucleus
  • Cercopithecus aethiops
  • DNA-Binding Proteins
  • Endocytosis
  • Lipid Metabolism
  • Male
  • Molecular Sequence Data
  • Mutation
  • Nuclear Localization Signals
  • Prostatic Neoplasms
  • Protein Transport
  • RNA Interference
  • Receptors, Androgen
  • Response Elements
  • Transcription, Genetic

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