内输蛋白
核运输
生物
端粒酶逆转录酶
核定位序列
NLS公司
磷酸化
细胞生物学
核蛋白
核出口信号
端粒酶
细胞核
生物化学
细胞质
转录因子
基因
作者
Sun Ah Jeong,Kuglae Kim,Ji Hoon Lee,Jeong Ho Seok,Prabhat Khadka,Hyun‐Soo Cho,In Kwon Chung
摘要
ABSTRACT Telomeres are essential for chromosome integrity and protection, and their maintenance requires the ribonucleoprotein enzyme telomerase. Previously, we have shown that human telomerase reverse transcriptase (hTERT) contains a bipartite nuclear localization signal (NLS; residues 222–240) that is responsible for nuclear import, and that Akt-mediated phosphorylation of residue S227 is important for efficient nuclear import of hTERT. Here, we show that hTERT binds to importin-α proteins through the bipartite NLS and that this heterodimer then forms a complex with importin-β proteins to interact with the nuclear pore complex. Depletion of individual importin-α proteins results in a failure of hTERT nuclear import, and the resulting cytoplasmic hTERT is degraded by ubiquitin-dependent proteolysis. Crystallographic analysis reveals that the bipartite NLS interacts with both the major and minor sites of importin-α proteins. We also show that Akt-mediated phosphorylation of S227 increases the binding affinity for importin-α proteins and promotes nuclear import of hTERT, thereby resulting in increased telomerase activity. These data provide details of a binding mechanism that enables hTERT to interact with the nuclear import receptors and of the control of the dynamic nuclear transport of hTERT through phosphorylation.
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