title: Human Telomerase Reverse Transcriptase (hTERT) Positively Regulates 26S Proteasome Activity.
abstract: Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, an RNA-dependent DNA polymerase that elongates telomeric DNA. hTERT displays several extra-telomeric functions that are independent of its telomere-regulatory function, including tumor progression, and neuronal cell death regulation. In this study, we evaluated these additional hTERT non-telomeric functions. We determined that hTERT interacts with several 19S and 20S proteasome subunits. The 19S regulatory particle and 20S core particle are part of 26S proteasome complex, which plays a central role in ubiquitin-dependent proteolysis. In addition, hTERT positively regulated 26S proteasome activity independent of its enzymatic activity. Moreover, hTERT enhanced subunit interactions, which may underlie hTERT's ability of hTERT to stimulate the 26S proteasome. Furthermore, hTERT displayed cytoprotective effect against ER stress via the activation of 26S proteasome in acute myeloid leukemia cells. Our data suggest that hTERT acts as a novel chaperone to promote 26S proteasome assembly and maintenance. J. Cell. Physiol. 232: 2083-2093, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Im
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Jong Bok
authors.initials: JB
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Han-Woong
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Chung
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D059748:Proteolysis; D012313:RNA / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D016601:RNA-Binding Proteins; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014415:Tunicamycin / Q000494:pharmacology; D054875:Ubiquitination
chemical_list: D018832:Molecular Chaperones; C498506:PSMD4 protein, human; D061988:Proteasome Inhibitors; D016601:RNA-Binding Proteins; C422952:telomerase RNA; D014415:Tunicamycin; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse; C488165:PSMA3 protein, human; C576985:PSMA5 protein, human; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C119011:26S proteasome non-ATPase regulatory subunit 13