| Autor: |
Kweon, Tae Hyun, Jung, Hyeryeon, Ko, Jeong Yeon, Kang, Jingu, Kim, Wonyoung, Kim, Yeolhoe, Kim, Han Byeol, Yi, Eugene C., Ku, Nam-On, Cho, Jin Won, Yang, Won Ho |
| Zdroj: |
Cell Reports; May2024, Vol. 43 Issue 5, pN.PAG-N.PAG, 1p |
| Abstrakt: |
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. [Display omitted] • RBM14 regulates OGA protein level by facilitating its interaction with E3 ligase TRIM33 • RBM14 is O-GlcNAcylated on serine 521 by OGT • O -GlcNAcylation of RBM14 promotes degradation of OGA, elevating cellular O -GlcNAc • RBM14 O -GlcNAcylation promotes cancer cell growth, migration, and invasion Kweon et al. report that RBM14 contributes to elevated O -GlcNAcylation in cancer by promoting the degradation of OGA. RBM14 O -GlcNAcylation on serine 521 plays a critical role in this process by recruiting E3 ligase TRIM33 to OGA. Finally, O -GlcNAcylation of RBM14 is shown to modulate cancer cell growth, migration, and invasion. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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