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

J Cell Biol. 2005 Jul 18;170(2):191-200. doi: 10.1083/jcb.200503106.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • DNA-Binding Proteins
  • HIP1 protein, human
  • Nuclear Localization Signals
  • Receptors, Androgen