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Differential Regulation of Telomerase Reverse Transcriptase Promoter Activation and Protein Degradation by Histone Deacetylase Inhibition
Author(s) -
Qing Hua,
Aono Jun,
Findeisen Hannes M.,
Jones Karrie L.,
Heywood Elizabeth B.,
Bruemmer Dennis
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25226
Subject(s) - telomerase reverse transcriptase , histone deacetylase , telomere , telomerase , transcription (linguistics) , microbiology and biotechnology , biology , reverse transcriptase , histone deacetylase 5 , histone , chemistry , biochemistry , rna , dna , gene , linguistics , philosophy
Telomerase reverse transcriptase (TERT) maintains telomeres and is rate limiting for replicative life span. While most somatic tissues silence TERT transcription resulting in telomere shortening, cells derived from cancer or cardiovascular diseases express TERT and activate telomerase. In the present study, we demonstrate that histone deacetylase (HDAC) inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Finally, we demonstrate that HDAC inhibition decreases TERT expression during vascular remodeling in vivo. These data illustrate a differential regulation of TERT transcription and protein stability by HDAC inhibition and suggest that TERT may constitute an important target for the anti‐proliferative efficacy of HDAC inhibitors. J. Cell. Physiol. 231: 1276–1282, 2016. © 2015 Wiley Periodicals, Inc.