视黄醇X受体
核运输
内输蛋白
核定位序列
核受体
肝X受体
交易激励
NLS公司
生物
细胞生物学
转录因子
核受体辅阻遏物1
核受体辅活化子1
小异二聚体伴侣
视黄醇X受体α
细胞核
生物化学
基因
细胞质
作者
Anna M. Miller,Christine Crumbley,Kirsten Prüfer
标识
DOI:10.1016/j.biocel.2008.08.016
摘要
Liver X receptors (LXRs) alpha and beta are nuclear receptors, which form obligate heterodimers with the retinoid X receptor (RXR). The LXRs regulate both redundantly and non-redundantly the transcription of genes controlling cholesterol metabolism and transport as well as lipogenesis. Previously, we showed that mutations in putative N-terminal nuclear localization sequences (NLSs) within both LXRs inhibit nuclear import. Through in vitro studies, we show here that these NLSs bind importin alpha and are both necessary and sufficient for the nuclear import of LXRs. Imaging, transactivation, and electro-mobility shift experiments show that RXR rescues the nuclear import of the LXRalpha NLS mutant yet does not restore its transcriptional activity despite intact DNA binding. In contrast, RXR partially rescues the import of the LXRbeta NLS mutant, but has no effect on its transcriptional activity due to the loss of DNA binding. Experiments with NLS mutant RXR confirmed that RXR may dominate the nuclear import of the RXR/LXRalpha heterodimer, whereas LXRbeta dominates the nuclear import of the RXR/LXRbeta heterodimer. Intriguingly, our data indicate differences between LXRalpha and LXRbeta in their interaction with RXR and in the role their NLSs play in transactivating functions independent of nuclear import.
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