Exploring the mechanism of inhibition of human telomerase by cysteine-reactive compounds.

Abstract:

:Telomerase is an almost universal cancer target that consists minimally of a core protein human telomerase reverse transcriptase (hTERT) and a RNA component human telomerase RNA (hTR). Some inhibitors of this enzyme are thought to function by the covalent binding to one or several cysteine residues; however, this inhibition mechanism has never been investigated because of the difficulty in producing telomerase. In this study, we use a recent method to produce recombinant hTERT to analyze the effect of cysteine-reactive inhibitors on telomerase. Using mass spectrometry and mutagenesis analysis, we identify several targeted residues in separated domains of the hTERT protein and show that cysteine-reactive reagents abolish the interaction with the CR4/5 region of hTR.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Kellermann G,Dingli F,Masson V,Dauzonne D,Ségal-Bendirdjian E,Teulade-Fichou MP,Loew D,Bombard S

doi

10.1002/1873-3468.12589

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

863-874

issue

6

eissn

0014-5793

issn

1873-3468

journal_volume

591

pub_type

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