Active, interactive, and inactive steroid receptor mutants.
In transient co-transfection assays, there is extensive cross-interaction between glucocorticoid receptor (GR) domains. For example, mutation of the conserved Ile residue at position 484 (rat GR map) to cysteine allows a net separation of transactivation and DNA binding. We also observed that the ligand binding domain plays a key role in cooperative transactivation. Furthermore, some carboxy-located mutations markedly alter the response of GR to agonists and antagonists. Finally, different reading frames of the CAG repeat that normally produces an amino-located poly-Gln repeat profoundly affect GR transactivation without altering DNA or ligand binding. This trans-dominant negative phenotype, seen when the CAG repeat yields a poly-Ala stretch, may turn out to be an excellent tool for functional analysis of GR in transgenic organisms.
Lanz
R B
RB
Institüt für Molekularbiologie II der Universität Zürich, Switzerland.
Hug
M
M
Gola
M
M
Tallone
T
T
Wieland
S
S
Rusconi
S
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015533:Transcriptional Activation; D014162:Transfection; D016335:Zinc Fingers
D011965:Receptors, Glucocorticoid; D004247:DNA