Differential Regulation of Telomerase Reverse Transcriptase Promoter Activation and Protein Degradation by Histone Deacetylase Inhibition.
Author: Qing H1,2,3, Aono J1, Findeisen HM1, Jones KL1, Heywood EB1, Bruemmer D1,2.
Affiliation:
1Saha Cardiovascular Research Center, University of Kentucky, Lexington, 40536. 2Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, 40536. 3Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Conference/Journal: J Cell Physiol.
Date published: 2015 Oct 27
Other:
Special Notes: doi: 10.1002/jcp.25226 , Word Count: 152
Abstract
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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
HDAC inhibitors; Neointima; Telomerase reverse transcriptase; Vascular smooth muscle cell
PMID: 26505494
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