Pathologic human GR mutant has a transdominant negative effect on the wild-type GR by inhibiting its translocation into the nucleus: importance of the ligand-binding domain for intracellular GR trafficking.

@article{Kino2001PathologicHG,
  title={Pathologic human GR mutant has a transdominant negative effect on the wild-type GR by inhibiting its translocation into the nucleus: importance of the ligand-binding domain for intracellular GR trafficking.},
  author={Tomoshige Kino and Roland H. Stauber and James H. Resau and George N Pavlakis and George P. Chrousos},
  journal={The Journal of clinical endocrinology and metabolism},
  year={2001},
  volume={86 11},
  pages={5600-8}
}
The syndrome of familial or sporadic glucocorticoid resistance is characterized by hypercortisolism without the clinical stigmata of Cushing syndrome. This condition is usually caused by mutations of the human GR, a ligand-activated transcription factor that shuttles between the cytoplasm and the nucleus. A pathological human mutant receptor, in which Ile was replaced by Asn at position 559, had negligible ligand binding, was transcriptionally extremely weak, and exerted a transdominant… CONTINUE READING