State Key Lab of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
Traffic. 2012 Jun;13(6):790-9. doi: 10.1111/j.1600-0854.2012.01346.x. Epub 2012 Mar 14.
HSCARG is a newly identified nuclear factor-κB (NF-κB) inhibitor that plays important roles in cell growth. Our previous study found that HSCARG could shuttle between the nucleus and cytoplasm by sensing the change in cellular redox states. To further investigate the mechanism of HSCARG translocation and its effect on the regulation of NF-κB activity, we identified a previously uncharacterized nuclear export signal (NES) at residues 272-278 of HSCARG that is required for its cytoplasmic translocation. This leucine-rich NES was found to be mediated by chromosome region maintenance 1. More importantly, accumulation of HSCARG in the nucleus occurred following a mutation in the NES or oxidative stress, which attenuated the inhibition of NF-κB by HSCARG. These results indicate that nucleocytoplasmic translocation of HSCARG plays an important role in fine-tuning NF-κB signaling.
HSCARG 是一种新鉴定的核因子-κB（NF-κB）抑制剂，在细胞生长中发挥重要作用。我们之前的研究发现，HSCARG 可以通过感知细胞氧化还原状态的变化在核质间穿梭。为了进一步研究 HSCARG 易位的机制及其对 NF-κB 活性的调节作用，我们在 HSCARG 的 272-278 位残基中鉴定到一个以前未被描述的核输出信号（NES），该信号对于其细胞质易位是必需的。这个富含亮氨酸的 NES 被发现是由染色体区域维持 1 介导的。更重要的是，在 NES 突变或氧化应激下，HSCARG 在核内的积累增加，从而减弱了 HSCARG 对 NF-κB 的抑制作用。这些结果表明，HSCARG 的核质易位在精细调节 NF-κB 信号中发挥重要作用。
