4b18

Publication Abstract from PubMed

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-alpha proteins through the bipartite NLS and that this heterodimer then forms a complex with importin-beta proteins to interact with the nuclear pore complex. Depletion of individual importin-alpha 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-alpha proteins. We also show that Akt-mediated phosphorylation of S227 increases the binding affinity for importin-alpha 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.

Akt-mediated phosphorylation increases the binding affinity of hTERT for importin alpha to promote nuclear translocation.,Jeong SA, Kim K, Lee JH, Cha JS, Khadka P, Cho HS, Chung IK J Cell Sci. 2015 Jun 15;128(12):2287-301. doi: 10.1242/jcs.166132. Epub 2015 May , 21. PMID:25999477^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.