Serine/threonine-protein phosphatase 2A physically interacts with human telomerase reverse transcriptase hTERT and regulates its subcellular distribution
Article first published online: 17 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 2, pages 409–417, February 2013
How to Cite
Xi, P., Zhou, L., Wang, M., Liu, J.-P. and Cong, Y.-S. (2013), Serine/threonine-protein phosphatase 2A physically interacts with human telomerase reverse transcriptase hTERT and regulates its subcellular distribution. J. Cell. Biochem., 114: 409–417. doi: 10.1002/jcb.24378
- Issue published online: 17 DEC 2012
- Article first published online: 17 DEC 2012
- Accepted manuscript online: 7 SEP 2012 07:55AM EST
- Manuscript Accepted: 27 AUG 2012
- Manuscript Received: 19 MAY 2012
- National Natural Science Foundation of China. Grant Numbers: 31071200, 31171320
- National Basic Research Program of China. Grant Number: 2012CB911203
Telomerase plays fundamental roles in bypassing cellular aging and promoting cancer progression by maintaining telomere homeostasis and telomere-independent activities. However, the molecular mechanisms by which telomerase provokes aging and cancer are far from being fully understood. In a search for proteins interacting with human telomerase reverse transcriptase hTERT by the yeast two-hybrid screen using hTERT T-motif as bait, we identified PP2A scaffolding subunit PR65 alpha isoform as an hTERT interacting partner. We showed that both PP2A catalytic subunit PP2AC and scaffolding subunit PR65 interacted with hTERT in vivo and in vitro and inhibited telomerase activity. In addition, we found that PP2A prevented the interaction of hTERT with 14-3-3θ signaling protein, an hTERT binding partner that is required for nuclear localization of hTERT. Activation of PP2A by overexpression of PP2AC or PR65 led to cytoplasmic accumulation of hTERT, which was reversed by treatment with PP2A inhibitor okadaic acid. Together, these observations suggest that PP2A regulates hTERT subcellular localization, in addition to its inhibitory effects on telomerase activity. J. Cell. Biochem. 114: 409–417, 2013. © 2012 Wiley Periodicals, Inc.