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.

journal_name

Sci Adv

journal_title

Science advances

authors

Perera ON,Sobinoff AP,Teber ET,Harman A,Maritz MF,Yang SF,Pickett HA,Cesare AJ,Arthur JW,MacKenzie KL,Bryan TM

doi

10.1126/sciadv.aav4409

subject

Has Abstract

pub_date

2019-10-02 00:00:00

pages

eaav4409

issue

10

issn

2375-2548

pii

aav4409

journal_volume

5

pub_type

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