文章基本信息

标题：Transportin-2 plays a critical role in nucleocytoplasmic shuttling of oestrogen receptor-α
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作者：Tetsuji Moriyama ; Yoshihiro Yoneda ; Masahiro Oka 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
页码：1-17
DOI：10.1038/s41598-020-75631-3
出版社：Springer Nature
摘要：Oestrogen receptor-α (ERα) 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 ERα nucleocytoplasmic shuttling. In this study, we found that ERα is transported into the nucleus by importin-α/β1. Furthermore, we found that Transportin-2 (TNPO2) is involved in 17β-oestradiol (E2)-dependent cytoplasmic localisation of ERα. Interestingly, it was found that TNPO2 does not mediate nuclear export, but rather is involved in the cytoplasmic retention of ERα via the proline/tyrosine (PY) motifs. Moreover, we found that TNPO2 competitively binds to the basic nuclear localisation signal (NLS) of ERα with importin-α to inhibit importin-α/β-dependent ERα nuclear import. Finally, we confirmed that TNPO2 knockdown enhances the nuclear localisation of wild-type ERα and reduces PI3K/AKT phosphorylation in the presence of E2. These results reveal that TNPO2 regulates nucleocytoplasmic shuttling and cytoplasmic retention of ERα, so that ERα has precise functions depending on the stimulation.
其他摘要：Abstract Oestrogen receptor-α (ERα) 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 ERα nucleocytoplasmic shuttling. In this study, we found that ERα is transported into the nucleus by importin-α/β1. Furthermore, we found that Transportin-2 (TNPO2) is involved in 17β-oestradiol (E2)-dependent cytoplasmic localisation of ERα. Interestingly, it was found that TNPO2 does not mediate nuclear export, but rather is involved in the cytoplasmic retention of ERα via the proline/tyrosine (PY) motifs. Moreover, we found that TNPO2 competitively binds to the basic nuclear localisation signal (NLS) of ERα with importin-α to inhibit importin-α/β-dependent ERα nuclear import. Finally, we confirmed that TNPO2 knockdown enhances the nuclear localisation of wild-type ERα and reduces PI3K/AKT phosphorylation in the presence of E2. These results reveal that TNPO2 regulates nucleocytoplasmic shuttling and cytoplasmic retention of ERα, so that ERα has precise functions depending on the stimulation.