The putative tumor suppressor C53 interacts with the human telomerase reverse transcriptase hTERT and regulates telomerase activity

Abstract

Telomerase is a large ribonucleoprotein complex that contains a catalytic telomerase reverse transcriptase (TERT) and an RNA template. Telomerase activity is tightly controlled by TERT expression, which is regulated at both the transcriptional and post-translational levels. However, the detailed molecular mechanisms of telomerase regulation and function are not fully understood. To identify cofactors that contribute to telomerase regulation, we employed a yeast two-hybrid system to screen for hTERT-interacting proteins, using the hTERT T-motif as bait. We identify C53 as a novel hTERT interaction partner. We show that C53 interacts with hTERT both in vivo and in vitro. C53 depletion increases telomerase activity, and C53 overexpression inhibits telomerase activity in MCF7 cells. In addition, the C53 leucine zipper domain (amino acids 301–400) is required for interaction with hTERT. Deleting the leucine zipper domain eliminates C53 interaction with hTERT and abrogates its inhibitory effect on telomerase activity. Taken together, our results demonstrate that C53 is a novel hTERT-associated protein that negatively regulates telomerase activity.