Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors.
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Mills IG, Gaughan L, Robson C, Ross T, McCracken S, Kelly J, Neal DE
Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors.
J Cell Biol. 2005 Jul 18;170(2):191-200.
- PubMed ID
- 16027218 [ View in PubMed]
- 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.