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

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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, I 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 (US)
Pages (from-to)191-200
Number of pages10
JournalJournal of Cell Biology
Volume170
Issue number2
DOIs
Publication statusPublished - Jul 2005

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ASJC Scopus subject areas

  • Cell Biology

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