The human telomeric protein TRF2 protects chromosome ends by facilitating their organization into the protective capping structure. Here we show that the stability of TRF2 is regulated via modification by the small ubiquitin-like modifiers (SUMO). TRF2 specifically interacts with and is sumoylated by PIAS1 in mammalian cells. The proteasome inhibitor stabilizes SUMO-conjugated TRF2 without affecting the level of unmodified TRF2, suggesting that SUMO conjugation is required for proteasomal degradation of TRF2. We also show that RNF4, a mammalian SUMO-targeted ubiquitin ligase, interacts with TRF2 in a SUMO-dependent manner and preferentially targets SUMO-conjugated TRF2 for ubiquitination. Collectively, our data demonstrate that the PIAS1-mediated sumoylation status of TRF2 serves as a molecular switch that controls the level of TRF2 at telomeres.
Bibliographical noteFunding Information:
This study was supported by a Grant from the Bio & Medical Technology Development Program of the National Research Foundation funded by the Korean Ministry of Science, ICT, and Future Planning (No. 2013M3A9B6076413 ) and a Grant from Yonsei University (No. 2014-22-0096 ).
© 2015 Federation of European Biochemical Societies.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Cell Biology