The human telomeric protein TRF1 negatively regulates telomere length by inhibiting the access of telomerase to telomeres. Here, we describe a novel function of NEDD8 ultimate buster-1 (NUB1) for regulating the levels of TRF1 at telomeres. NUB1 is a NEDD8-interacting protein, which down-regulates the NEDD8 conjugation system. We showed that NUB1 physically interacts with TRF1 and promotes its degradation by the proteasome in the absence of NEDD8 conjugation. We also demonstrated that TRF1 is conjugated to NEDD8, and that neddylated TRF1 is targeted to the proteasome for degradation in a NUB1-dependent manner. These data suggest that NUB1 participates in telomere maintenance by regulating the levels of TRF1 at telomeres through both NEDD8-dependent and NEDD8-independent pathways.
Bibliographical noteFunding Information:
We thank Dr Titia de Lange at Rockefeller University for kindly providing anti-TRF1 antibody. 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).
© 2016 Federation of European Biochemical Societies
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Cell Biology