Telomerase promotes formation of a telomere protective complex in cancer cells.

Abstract	Telomerase is a ribonucleoprotein complex that catalyzes addition of telomeric DNA repeats to maintain telomeres in replicating cells. Here, we demonstrate that the telomerase protein hTERT performs an additional role at telomeres that is independent of telomerase catalytic activity yet essential for telomere integrity and cell proliferation. Short-term depletion of endogenous hTERT reduced the levels of heat shock protein 70 (Hsp70-1) and the telomere protective protein Apollo at telomeres, and induced telomere deprotection and cell cycle arrest, in the absence of telomere shortening. Short-term expression of hTERT promoted colocalization of Hsp70-1 with telomeres and Apollo and reduced numbers of deprotected telomeres, in a manner independent of telomerase catalytic activity. These data reveal a previously unidentified noncanonical function of hTERT that promotes formation of a telomere protective complex containing Hsp70-1 and Apollo and is essential for sustained proliferation of telomerase-positive cancer cells, likely contributing to the known cancer-promoting effects of both hTERT and Hsp70-1.
Authors	Omesha N Perera, Alexander P Sobinoff, Erdahl T Teber, Ashley Harman, Michelle F Maritz, Sile F Yang, Hilda A Pickett, Anthony J Cesare, Jonathan W Arthur, Karen L MacKenzie, Tracy M Bryan
Journal	Science advances (Sci Adv) Vol. 5 Issue 10 Pg. eaav4409 (10 2019) ISSN: 2375-2548 [Electronic] United States
PMID	31616780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Chemical References	BIRC6 protein, human HSP70 Heat-Shock Proteins Hspa14 protein, human Inhibitor of Apoptosis Proteins TERT protein, human Telomerase
Topics	Cell Line, Tumor DNA Damage Gene Expression Regulation HSP70 Heat-Shock Proteins (genetics, metabolism) Humans Inhibitor of Apoptosis Proteins (genetics, metabolism) Neoplasms (genetics, metabolism) Telomerase (genetics, metabolism) Telomere (metabolism)

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