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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 publication

DOI

10.1083/jcb.200503106

Type

Journal article

Journal

J Cell Biol

Publication Date

18/07/2005

Volume

170

Pages

191 - 200

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