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

2005 ◽  
Vol 170 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Ian G. Mills ◽  
Luke Gaughan ◽  
Craig Robson ◽  
Theodora Ross ◽  
Stuart McCracken ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Hormone Receptors ◽  
Nuclear Translocation ◽  
Coiled Coil ◽  
Adaptor Proteins ◽  
Cellular Transformation ◽  
Interacting Protein ◽  
Response Elements ◽  
Huntingtin Interacting Protein 1 ◽  
Huntingtin Interacting Protein

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.

scholarly journals It's HIP to be a hub

2005 ◽  
Vol 170 (2) ◽  
pp. 169-171 ◽  
Author(s):  
Manuela Vecchi ◽  
Pier Paolo Di Fiore
Keyword(s):  
Network Theory ◽  
Transcriptional Activity ◽  
Hormone Receptors ◽  
Nuclear Hormone Receptors ◽  
Interacting Protein ◽  
Endocytic Protein ◽  
Huntingtin Interacting Protein 1 ◽  
Huntingtin Interacting Protein ◽  
Endocytic Proteins

Many endocytic proteins shuttle between the nucleus and the cytoplasm; however, their putative function in the nucleus is unclear. Now, new data demonstrate that huntingtin interacting protein 1 (HIP1), an endocytic protein, modulates the transcriptional activity of nuclear hormone receptors. In network theory, therefore, HIP1 can be regarded as a hub connecting heterogeneous functional “territories:” a possibility with important physiological and pathological implications.

scholarly journals Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain

2010 ◽  
Vol 66 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Jeremy D. Wilbur ◽  
Peter K. Hwang ◽  
Frances M. Brodsky ◽  
Robert J. Fletterick
Keyword(s):  
Light Chain ◽  
Coiled Coil ◽  
Actin Binding ◽  
Interacting Protein ◽  
Similar Region ◽  
Coiled Coil Domain ◽  
Coiled Coil Region ◽  
Huntingtin Interacting Protein 1 ◽  
Conformational Regulation ◽  
Huntingtin Interacting Protein

Huntingtin-interacting protein 1 (HIP1) is an important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery. HIP1 has also been implicated in the pathogenesis of Huntington's disease. The binding of HIP1 to actin is regulated through an interaction with clathrin light chain. Clathrin light chain binds to a flexible coiled-coil domain in HIP1 and induces a compact state that is refractory to actin binding. To understand the mechanism of this conformational regulation, a high-resolution crystal structure of a stable fragment from the HIP1 coiled-coil domain was determined. The flexibility of the HIP1 coiled-coil region was evident from its variation from a previously determined structure of a similar region. A hydrogen-bond network and changes in coiled-coil monomer interaction suggest that the HIP1 coiled-coil domain is uniquely suited to allow conformational flexibility.

scholarly journals Clathrin binding to the DLLRKN region of Huntingtin‐interacting protein 1 (HIP1) requires coiled coil instability

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Joel Alcasid Ybe ◽  
Arun Alphonse Ignatius ◽  
David Giedroc ◽  
Melissa Illingworth ◽  
Sara Poorfarahani
Keyword(s):  
Coiled Coil ◽  
Interacting Protein ◽  
Huntingtin Interacting Protein 1 ◽  
Huntingtin Interacting Protein

scholarly journals β-Catenin Binds to the Activation Function 2 Region of the Androgen Receptor and Modulates the Effects of the N-Terminal Domain and TIF2 on Ligand-Dependent Transcription

2003 ◽  
Vol 23 (5) ◽  
pp. 1674-1687 ◽  
Author(s):  
Liang-Nian Song ◽  
Roger Herrell ◽  
Stephen Byers ◽  
Salimuddin Shah ◽  
Elizabeth M. Wilson ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Hormone Receptors ◽  
Nuclear Translocation ◽  
Retinoic Acid Receptor ◽  
Activation Function ◽  
Steroid Hormone Receptors ◽  
Binding Assays ◽  
Peptide Motifs ◽  
Terminal Domain ◽  
Helix 12

ABSTRACT β-Catenin is a multifunctional molecule that is activated by signaling through WNT receptors. β-Catenin can also enhance the transcriptional activity of some steroid hormone receptors such as the androgen receptor and retinoic acid receptor α. Androgens can affect nuclear translocation of β-catenin and influence its subcellular distribution. Using mammalian two-hybrid binding assays, analysis of reporter gene transcription, and coimmunoprecipitation, we now show that β-catenin binds to the androgen receptor ligand-binding domain (LBD) and modulates the transcriptional effects of TIF2 and the androgen receptor N-terminal domain (NTD). In functional assays, β-catenin bound to androgen receptor only in the presence of ligand agonists, not antagonists. β-Catenin binding to the androgen receptor LBD was independent of and cooperative with the androgen receptor NTD and the p160 coactivator TIF2, both of which bind to the activation function 2 (AF-2) region of the androgen receptor. Different mutations of androgen receptor helix 3 amino acids disrupted binding of androgen receptor NTD and β-catenin. β-Catenin, androgen receptor NTD, and TIF2 binding to the androgen receptor LBD were affected similarly by a subset of helix 12 mutations, but disruption of two sites on helix 12 affected only binding of β-catenin and not of TIF2 or the androgen receptor NTD. Mutational disruption of each of five LXXLL peptide motifs in the β-catenin armadillo repeats did not disrupt either binding to androgen receptor or transcriptional coactivation. ICAT, an inhibitor of T-cell factor 4 (TCF-4), and E-cadherin binding to β-catenin also blocked binding of the androgen receptor LBD. We also demonstrated cross talk between the WNT and androgen receptor signaling pathways because excess androgen receptor could interfere with WNT signaling and excess TCF-4 inhibited the interaction of β-catenin and androgen receptor. Taken together, the data show that β-catenin can bind to the androgen receptor LBD and modulate the effects of the androgen receptor NTD and TIF2 on transcription.

scholarly journals Huntingtin Interacting Protein 1 Induces Apoptosis via a Novel Caspase-dependent Death Effector Domain

2000 ◽  
Vol 275 (52) ◽  
pp. 41299-41308 ◽  
Author(s):  
Abigail S. Hackam ◽  
Ayman S. Yassa ◽  
Roshni Singaraja ◽  
Martina Metzler ◽  
Claire-Anne Gutekunst ◽  
...  
Keyword(s):  
Interacting Protein ◽  
Effector Domain ◽  
Death Effector Domain ◽  
Huntingtin Interacting Protein 1 ◽  
Death Effector ◽  
Huntingtin Interacting Protein
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