Akt-mediated phosphorylation increases the binding affinity of hTERT for importin α to promote nuclear translocation

Sun Ah Jeong, Kuglae Kim, Ji Hoon Lee, Jeong Seok Cha, Prabhat Khadka, Hyun Soo Cho, In Kwon Chung

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24 Citations (Scopus)


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 Aktmediated 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.

Original languageEnglish
Pages (from-to)2287-2301
Number of pages15
JournalJournal of cell science
Issue number12
Publication statusPublished - 2015

Bibliographical note

Publisher Copyright:
© 2015. Published by The Company of Biologists Ltd.

All Science Journal Classification (ASJC) codes

  • Cell Biology


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