Nucleolar modulation of TRF1: a dynamic way to regulate telomere and cell cycle by nucleostemin and GNL3L.
Nucleolar modulation of TRF1: a dynamic way to regulate telomere and cell cycle by nucleostemin and GNL3L.
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DOI：
10.4161/cc.8.18.9543
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发表时间：
2009-09-15
期刊：
影响因子：
--
通讯作者：
Tsai RY
中科院分区：
文献类型：
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作者：
Tsai RY
染色体末端受到一种称为端粒的高阶结构的保护。保持正确的端粒长度和结构对于分裂和非分裂细胞的生存都是至关重要的。值得注意的是，多蛋白端粒覆盖复合体的一个组成部分TRF1(端粒重复序列结合因子1)的靶向缺失会在胚胎第5-6天导致死亡，而没有明显的端粒缺陷，这增加了TRF1也可能在端粒外的月光下发生的可能性。本课题组的两项研究进一步加强了TRF1的端粒外联系，报道了TRF1可被两种核仁GTP结合蛋白结合和调节的发现，即核干素(NS)和鸟嘌呤核苷酸结合蛋白样3(GNL3L)，这两种蛋白对TRF1的蛋白质降解表现出明显相反的作用。特别是，GNL3L能够在有丝分裂过程中稳定TRF1蛋白，并促进中期到后期的转变。本文对GNL3L介导的TRF1调控如何对端粒和细胞周期产生一种新的动态控制进行了讨论，并通过比较NS和GNL3L的活性来推断其进化意义。
Chromosomal ends are protected by a high-order structure called telomere. Maintenance of correct telomere length and structure is critically important for the viability of both dividing and non-dividing cells. Notably, targeted deletion of a component of the multi-protein telomere-capping complex, TRF1 (telomeric repeat binding factor 1), causes lethality at embryonic day 5-6 without apparent telomere deficiency, raising the possibility that TRF1 may also moonlight outside the telomere. Further reinforcing the extra-telomeric tie of TRF1, two studies from our group have reported the findings that TRF1 can be bound and modulated by two nucleolar GTP-binding proteins, nucleostemin (NS) and guanine nucleotide binding protein-like 3 (GNL3L), which exhibit apparently opposite effects on the protein degradation of TRF1. In particular, GNL3L is able to stabilize TRF1 protein during mitosis and promote the metaphase-to-anaphase transition. This manuscript extends the discussion on how this GNL3L-mediated TRF1 regulation creates a novel dynamic control on telomere and cell cycle, and extrapolates its evolutionary significance by contrasting the activities of NS and GNL3L.