核仁与卷曲体磷酸化蛋白1（NOLC1）调节端粒重复结合因子2（TRF2）在核仁中的滞留。

Yuan Fuwen, Li Guodong, Tong Tanjun

Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing, China.

Cell Death Discov. 2017 Sep 4;3:17043. doi: 10.1038/cddiscovery.2017.43. eCollection 2017.

Telomeric repeat-binding factor 2 (TRF2) was reported to localize in the nucleolus of human cells in a cell cycle-dependent manner; however, the underlying mechanism remains unclear. Here, we found that nucleolar and coiled-body phosphoprotein 1 (NOLC1) interacted with TRF2 and mediated the shuttling of TRF2 between the nucleolus and nucleus in human 293T and HepG2 cells. Ablation of NOLC1 expression increased the number of nuclear TRF2 foci and decreased the nucleolar level of TRF2. Conversely, NOLC1 overexpression promoted the nucleolar accumulation of TRF2. NOLC1 overexpression also increased the number of 53BP1 foci and induced the DNA damage response. In addition, co-expression of TRF2 rescued NOLC1 overexpression-induced cell cycle arrest and apoptosis.

据报道，端粒重复序列结合因子2（TRF2）以细胞周期依赖性方式定位于人类细胞的核仁中；然而，其潜在机制仍不清楚。在这里，我们发现核仁与卷曲体磷蛋白1（NOLC1）与TRF2相互作用，并介导TRF2在人类293T和HepG2细胞的核仁和细胞核之间穿梭。NOLC1表达的缺失增加了核内TRF2灶的数量，并降低了TRF2的核仁水平。相反，NOLC1的过表达促进了TRF2在核仁中的积累。NOLC1的过表达还增加了53BP1灶的数量并诱导了DNA损伤反应。此外，TRF2的共表达挽救了NOLC1过表达诱导的细胞周期停滞和凋亡。