数字农科院2.0

UBE2S facilitates glioblastoma progression through activation of the NF-κB pathway via attenuating K11-linked ubiquitination of AKIP1

文献类型： 外文期刊

作者： Zhibin Han;Lin Xu;Aowen Wang;Baoju Wang;Qinfang Liu;Hongyang Liu;Qi Liu;Zhenbo Gang;Shengkun Yu;Long Mu;Changjiang Weng;Zhiguo Lin;Li Hu

作者机构：

关键词： AKIP1;Deubiquitination;GBM;NF-κB;UBE2S

期刊名称： International Journal of Biological Macromolecules

ISSN： 0141-8130

年卷期： 2024 年 278 卷

页码：

收录情况： SCIE（2024版） ; ; EI（2024版）

摘要： Background: Rapid proliferation is a hallmark of glioblastoma multiforme (GBM) and a major contributor to its recurrence. Aberrant ubiquitination has been implicated in various diseases, including cancer. In our preliminary studies, we identified Ubiquitin-conjugating enzyme E2S (UBE2S) as a potential glioma biomarker, exhibiting close associations with glioma grade and protein phosphatase 1, regulatory subunit 105 (Ki67) expression levels. However, the underlying molecular mechanisms remained elusive. NF-κB is an important signaling pathway that promotes GBM proliferation. Direct intervention targeting NF-κB has not yielded the expected results, prompting the exploration of new molecules for regulating NF-κB as a new direction. Methods: This study employed methods including yeast two-hybrid and immunoprecipitation to uncover the interaction between UBE2S and A kinase interacting protein 1 (AKIP1). Laser confocal microscopy was used to observe the localization of UBE2S and AKIP1. Dual luciferase reporter genes were utilized to observe the activation of NF-κB. Results: Our findings demonstrate that UBE2S deficiency significantly impedes GBM progression, both in vitro and in vivo. Mechanistically, UBE2S plays a crucial role in recruiting Ubiquitin Specific Peptidase 15 (USP15), facilitating the removal of K11-linked ubiquitination on AKIP1. This action enhances AKIP1 stability within the GBM context. The resulting increase in AKIP1 levels further augments nuclear factor kappa-B (NF-κB) transcriptional activity, leading to the upregulation of downstream genes regulated by the NF-κB pathway, thereby promoting GBM progression. Conclusions: In summary, our findings reveal the role of the UBE2S/AKIP1-NF-κB axis in regulating GBM progression and provide novel evidence supporting UBE2S as a potential drug target for GBM.

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