Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors.
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.
Mills
Ian G
IG
Cancer Research UK Uro-Oncology Research Group, Department of Oncology, University of Cambridge, Hutchison/Medical Research Council Cancer Research Centre, Cambridge CB2 2XZ, England, UK. igm23@cam.ac.uk
Gaughan
Luke
L
Robson
Craig
C
Ross
Theodora
T
McCracken
Stuart
S
Kelly
John
J
Neal
David E
DE
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D050356:Lipid Metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms; D021381:Protein Transport; D034622:RNA Interference; D011944:Receptors, Androgen / Q000378:metabolism*; D020218:Response Elements; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C073368:HIP1 protein, human; D019913:Nuclear Localization Signals; D011944:Receptors, Androgen