Priority Research Paper Volume 1, Issue 7 pp 608—621
Telomere length regulates ISG15 expression in human cells
- 1 Department of Cell Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
- 2 Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA
- 3 Current address: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
- 4 Department of Biotechnology, Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences, A-1190 Vienna, Austria
Received: June 15, 2009 Accepted: July 16, 2009 Published: July 17, 2009
https://doi.org/10.18632/aging.100066How to Cite
Abstract
Endogenous genes regulated by telomere length have not previously been identified in human cells. Here we show that telomere length regulates the expression of interferon stimulated gene 15 (ISG15, 1p36.33). ISG15 expression (RNA and protein) increases in human cells with short telomeres, and decreases following the elongation of telomeres by human telomerase reverse transcriptase (hTERT). The short-telomere-dependent up-regulation of ISG15 is not mediated by replicative senescence/DNA damage signaling or type I interferons. In human skin specimens obtained from various aged individuals, ISG15 is up-regulated in a subset of cells in older individuals. Our results demonstrate that endogenous human genes can be regulated by the length of telomeres prior to the onset of DNA damage signals, and suggest the possibility that cell turnover/telomere shortening may provide a mechanism for adjusting cellular physiology. The upregulation of ISG15 with telomere shortening may contribute to chronic inflammatory states associated with human aging.