Mutual regulation between OGT and XIAP to control colon cancer cell growth and invasion

Hyeon Gyu Seo, Han Byeol Kim, Ji Young Yoon, Tae Hyun Kweon, Yun Soo Park, Jingu Kang, Jinwoo Jung, Seong Jin Son, Eugene C. Yi, Tae Ho Lee, Won Ho Yang, Jin Won Cho

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number815
JournalCell Death and Disease
Volume11
Issue number9
DOIs
Publication statusPublished - 2020 Sept 1

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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