Transportin-2 plays a critical role in nucleocytoplasmic shuttling of oestrogen receptor-?.

ABSTRACT: Oestrogen receptor-? (ER?) shuttles continuously between the nucleus and the cytoplasm, and functions as an oestrogen-dependent transcription factor in the nucleus and as an active mediator of signalling pathways, such as phosphatidylinositol 3-kinase (PI3K)/AKT, in the cytoplasm. However, little is known regarding the mechanism of ER? nucleocytoplasmic shuttling. In this study, we found that ER? is transported into the nucleus by importin-?/?1. Furthermore, we found that Transportin-2 (TNPO2) is involved in 17?-oestradiol (E2)-dependent cytoplasmic localisation of ER?. Interestingly, it was found that TNPO2 does not mediate nuclear export, but rather is involved in the cytoplasmic retention of ER? via the proline/tyrosine (PY) motifs. Moreover, we found that TNPO2 competitively binds to the basic nuclear localisation signal (NLS) of ER? with importin-? to inhibit importin-?/?-dependent ER? nuclear import. Finally, we confirmed that TNPO2 knockdown enhances the nuclear localisation of wild-type ER? and reduces PI3K/AKT phosphorylation in the presence of E2. These results reveal that TNPO2 regulates nucleocytoplasmic shuttling and cytoplasmic retention of ER?, so that ER? has precise functions depending on the stimulation.

SUBMITTER: Moriyama T 

PROVIDER: S-EPMC7596556 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature