Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

J. Cell Biol. 170 (2): 191-200

Copyright © 2005 by the Rockefeller University Press.


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

Ian G. Mills1, Luke Gaughan2, Craig Robson2, Theodora Ross3, Stuart McCracken2, John Kelly1, , and David E. Neal1

1 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
2 Prostate Research Group, Northern Institute for Cancer Research, University of Newcastle upon Tyne, Medical School, Newcastle upon Tyne NE2 4HH, England, UK
3 Department of Internal Medicine and Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109

Correspondence to I.G. Mills: igm23{at}

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.

I.G. Mills and L. Gaughan contributed equally to this paper.

Abbreviations used in this paper: ANTH, AP180 NH2-terminal homology; AR, androgen receptor; ARE, androgen response element; ChIP, chromatin immunoprecipitation; HIP1, huntingtin interacting protein 1; PSA, prostate-specific antigen; siRNA, silencing RNA.

An integrative, translational approach to understanding rare and orphan genetically based diseases.
R. Hoehndorf, P. N. Schofield, and G. V. Gkoutos (2013)
Interface Focus 3, 20120055
   Abstract »    Full Text »    PDF »
Endocytosis and Signaling: Cell Logistics Shape the Eukaryotic Cell Plan.
S. Sigismund, S. Confalonieri, A. Ciliberto, S. Polo, G. Scita, and P. P. Di Fiore (2012)
Physiol Rev 92, 273-366
   Abstract »    Full Text »    PDF »
Transcription regulation of caspase-1 by R393 of HIPPI and its molecular partner HIP-1.
M. Banerjee, M. Datta, P. Majumder, D. Mukhopadhyay, and N. P. Bhattacharyya (2010)
Nucleic Acids Res. 38, 878-892
   Abstract »    Full Text »    PDF »
Wild-type but not mutant huntingtin modulates the transcriptional activity of liver X receptors.
M Futter, H Diekmann, E Schoenmakers, O Sadiq, K Chatterjee, and D C Rubinsztein (2009)
J. Med. Genet. 46, 438-446
   Abstract »    Full Text »    PDF »
Actin Binding by Hip1 (Huntingtin-interacting Protein 1) and Hip1R (Hip1-related Protein) Is Regulated by Clathrin Light Chain.
J. D. Wilbur, C.-Y. Chen, V. Manalo, P. K. Hwang, R. J. Fletterick, and F. M. Brodsky (2008)
J. Biol. Chem. 283, 32870-32879
   Abstract »    Full Text »    PDF »
ChIPping away at gene regulation.
C. E. Massie and I. G. Mills (2008)
EMBO Rep. 9, 337-343
   Abstract »    Full Text »    PDF »
Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity.
R. S. Atwal, J. Xia, D. Pinchev, J. Taylor, R. M. Epand, and R. Truant (2007)
Hum. Mol. Genet. 16, 2600-2615
   Abstract »    Full Text »    PDF »
Huntingtin-Interacting Protein 1 Influences Worm and Mouse Presynaptic Function and Protects Caenorhabditis elegans Neurons against Mutant Polyglutamine Toxicity.
J. A. Parker, M. Metzler, J. Georgiou, M. Mage, J. C. Roder, A. M. Rose, M. R. Hayden, and C. Neri (2007)
J. Neurosci. 27, 11056-11064
   Abstract »    Full Text »    PDF »
Degenerative phenotypes caused by the combined deficiency of murine HIP1 and HIP1r are rescued by human HIP1.
S. V. Bradley, T. S. Hyun, K. I. Oravecz-Wilson, L. Li, E. I. Waldorff, A. N. Ermilov, S. A. Goldstein, C. X. Zhang, D. G. Drubin, K. Varela, et al. (2007)
Hum. Mol. Genet. 16, 1279-1292
   Abstract »    Full Text »    PDF »
Huntingtin Interacting Protein 1 Is a Novel Brain Tumor Marker that Associates with Epidermal Growth Factor Receptor.
S. V. Bradley, E. C. Holland, G. Y. Liu, D. Thomas, T. S. Hyun, and T. S. Ross (2007)
Cancer Res. 67, 3609-3615
   Abstract »    Full Text »    PDF »
Identification of Putative Androgen Receptor Interaction Protein Modules: Cytoskeleton and Endosomes Modulate Androgen Receptor Signaling in Prostate Cancer Cells.
R. Jasavala, H. Martinez, J. Thumar, A. Andaya, A.-C. Gingras, J. K. Eng, R. Aebersold, D. K. Han, and M. E. Wright (2007)
Mol. Cell. Proteomics 6, 252-271
   Abstract »    Full Text »    PDF »
Altered endocytosis of epidermal growth factor receptor in androgen receptor positive prostate cancer cell lines.
L. Bonaccorsi, D. Nosi, M. Muratori, L. Formigli, G. Forti, and E. Baldi (2007)
J. Mol. Endocrinol. 38, 51-66
   Abstract »    Full Text »    PDF »
Deletion of the triplet repeat encoding polyglutamine within the mouse Huntington's disease gene results in subtle behavioral/motor phenotypes in vivo and elevated levels of ATP with cellular senescence in vitro.
E. B.D. Clabough and S. O. Zeitlin (2006)
Hum. Mol. Genet. 15, 607-623
   Abstract »    Full Text »    PDF »
Cortical Recruitment and Nuclear-Cytoplasmic Shuttling of Scd5p, a Protein Phosphatase-1-targeting Protein Involved in Actin Organization and Endocytosis.
J. S. Chang, K. Henry, M. I. Geli, and S. K. Lemmon (2006)
Mol. Biol. Cell 17, 251-262
   Abstract »    Full Text »    PDF »
It's HIP to be a hub: new trends for old-fashioned proteins.
M. Vecchi and P. P. Di Fiore (2005)
J. Cell Biol. 170, 169-171
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882