ステロイドホルモン受容体の動態

抄録

With the advent of green fluorescent protein (GFP) and its color variants, the subcellular distribution of many steroid hormone receptors has been found to be much more dynamic than previously thought. FRET (fluorescence resonance energy transfer) clearly showed the interaction of estrogen receptor (ER) a and ERb. In the presence of the estradiol, however, the discrete staining pattern of ERa and b were overlapped with Brg-1, indicating that most of the ER clusters are involved in the chromatin remodeling machinery. FRAP (fluorescence recovery after photobleaching) analysis showed that nuclear ERa and b_ are mobile in the absence of the ligand, but its mobility was slightly decreased after the ligand treatment. Glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are localized in the cytoplasm in the absence of the ligand and they translocate to the nucleus after ligand binding. FRET demonstrated that importin a is involved in GR/MR translocation from the cytoplasm to the nucleus and GR and MR dimerize within the nucleus. FRAP showed that the movement of ligand-binded GR/MR is restricted in the nucleus. Steroid hormone receptor is composed of a transactivation domain (NTD), a DNA binding domain (DBD) and a ligand binding domain (LBD). Androgen receptor (AR) was chosen to investigate the domain specific nuclear import. Nuclear localization signal (NLS) of DBD was Ran- and importin a/b-dependent, whereas the NLS signal of NTD and LBD were Ran-dependent but importin-a/b independent, suggesting that the nuclear import of AR is regulated by the interplay between each domain of receptor. [J Physiol Sci. 2008;58 Suppl:S14]