title: Serine/threonine-protein phosphatase 2A physically interacts with human telomerase reverse transcriptase hTERT and regulates its subcellular distribution.
abstract: 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.
authors.affiliation: Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xi
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Liu
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Cong
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence / Q000187:drug effects; D005092:Exonucleases / Q000378:metabolism; D005095:Exoribonucleases; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D019319:Okadaic Acid; C509186:TERT protein, human; D019098:Telomerase; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2