Intracellular colocalization of HAP1/STBs with steroid hormone receptors and its enhancement by a proteasome inhibitor

Exp Cell Res. 2011 Jul 15;317(12):1689-700. doi: 10.1016/j.yexcr.2011.05.004. Epub 2011 May 14.


The stigmoid body (STB) is a cytoplasmic inclusion containing huntingtin-associated protein 1 (HAP1), and HAP1/STB formation is induced by transfection of the HAP1 gene into cultured cells. In the present study, we examined the intracellular colocalization of HAP1/STBs with steroid hormone receptors (SHRs), including the androgen receptor (AR), estrogen receptor, glucocorticoid receptor (GR), and mineralocorticoid receptor, in COS-7 cells cotransfected with HAP1 and each receptor. We found that C-terminal ligand-binding domains of all SHRs had potential for colocalization with HAP1/STBs, whereas only AR and GR were clearly colocalized with HAP1/STBs when each full-length SHR was coexpressed with HAP1. In addition, it appeared that HAP1/STBs did not disrupt GR and AR functions because the receptors on HAP1/STBs maintained nuclear translocation activity in response to their specific ligands. When the cells were treated with a proteasome inhibitor, GR and AR localized outside HAP1/STBs translocated into the nucleus, whereas the receptors colocalized with HAP1/STBs persisted in their colocalization even after treatment with their ligands. Therefore, HAP1/STBs may be involved in cytoplasmic modifications of the nuclear translocation of GR and AR in a ubiquitin-proteasome system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • COS Cells
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • Cysteine Proteinase Inhibitors / pharmacology
  • Fluorescent Antibody Technique
  • Humans
  • Immunoenzyme Techniques
  • Immunoprecipitation
  • Inclusion Bodies / drug effects*
  • Inclusion Bodies / metabolism
  • Leupeptins / pharmacology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Receptors, Mineralocorticoid / genetics
  • Receptors, Mineralocorticoid / metabolism*
  • Subcellular Fractions
  • Transcriptional Activation


  • AR protein, human
  • Cysteine Proteinase Inhibitors
  • HAP1 protein, human
  • Leupeptins
  • Nerve Tissue Proteins
  • Receptors, Androgen
  • Receptors, Estrogen
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde