O-GlcNAc transferase (OGT) is an enzyme that catalyzes the O-GlcNAc modification of nucleocytoplasmic proteins and is highly expressed in many types of cancer. However, the mechanism regulating its expression in cancer cells is not well understood. This study shows that OGT is a substrate of the E3 ubiquitin ligase X-linked inhibitor of apoptosis (XIAP) which plays an important role in cancer pathogenesis. Although LSD2 histone demethylase has already been reported as an E3 ubiquitin ligase in lung cancer cells, we identified XIAP as the main E3 ubiquitin ligase in colon cancer cells. Interestingly, OGT catalyzes the O-GlcNAc modification of XIAP at serine 406 and this modification is required for the E3 ubiquitin ligase activity of XIAP toward specifically OGT. Moreover, O-GlcNAcylation of XIAP suppresses colon cancer cell growth and invasion by promoting the proteasomal degradation of OGT. Therefore, our findings regarding the reciprocal regulation of OGT and XIAP provide a novel molecular mechanism for controlling cancer growth and invasion regulated by OGT and O-GlcNAc modification.
|Journal||Cell Death and Disease|
|Publication status||Published - 2020 Sept 1|
Bibliographical noteFunding Information:
We are grateful to Yanhui Xu at Fudan University (Shanghai, China) for providing the GST-OGT construct. This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2015M3A9B6073840 and NRF-2016R1A5A1010764) to
J.W.C. and E.C.Y. This research was also supported by the Andang Scholarship Foundation to H.G.S. and J.W.C.
© 2020, The Author(s).
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research