O-GlcNAcylation of RBM14 contributes to elevated cellular O-GlcNAc through regulation of OGA protein stability

Tae Hyun Kweon, Hyeryeon Jung, Jeong Yeon Ko, Jingu Kang, Wonyoung Kim, Yeolhoe Kim, Han Byeol Kim, Eugene C. Yi, Nam On Ku, Jin Won Cho, Won Ho Yang

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Dysregulation of O-GlcNAcylation has emerged as a potential biomarker for several diseases, particularly cancer. The role of OGT (O-GlcNAc transferase) in maintaining O-GlcNAc homeostasis has been extensively studied; nevertheless, the regulation of OGA (O-GlcNAcase) in cancer remains elusive. Here, we demonstrated that the multifunctional protein RBM14 is a regulator of cellular O-GlcNAcylation. By investigating the correlation between elevated O-GlcNAcylation and increased RBM14 expression in lung cancer cells, we discovered that RBM14 promotes ubiquitin-dependent proteasomal degradation of OGA, ultimately mediating cellular O-GlcNAcylation levels. In addition, RBM14 itself is O-GlcNAcylated at serine 521, regulating its interaction with the E3 ligase TRIM33, consequently affecting OGA protein stability. Moreover, we demonstrated that mutation of serine 521 to alanine abrogated the oncogenic properties of RBM14. Collectively, our findings reveal a previously unknown mechanism for the regulation of OGA and suggest a potential therapeutic target for the treatment of cancers with dysregulated O-GlcNAcylation.

Original languageEnglish
Article number114163
JournalCell Reports
Volume43
Issue number5
DOIs
Publication statusPublished - 2024 May 28

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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