OTUB1通过拮抗TRIM21诱导鞘氨醇激酶1（SPHK1）去泛素化，从而促进肝细胞癌进展。

OTUB1 antagonizes TRIM21 to induce deubiquitination of SPHK1 and promote the progression of hepatocellular carcinoma.

作者信息

Sun Chen, Cai Shuang, Yang Jun, Du Mingyang, Pan Qi, Wang Yutao, Sun Wei, Bai Ming, Liang Hongyuan

机构信息

Department of Interventional Radiology, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Gastroenterology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

出版信息

Oncogene. 2025 Aug 30. doi: 10.1038/s41388-025-03556-0.

DOI:10.1038/s41388-025-03556-0

PMID:40885853

Abstract

SPHK1 is critical for maintaining cellular lipid balance. Aberrant expression of SPHK1 aggravates malignancy of tumor through multiple signaling pathways. Here, we report a novel regulatory mechanism in ubiquitination of SPHK1. It is demonstrated that TRIM21 facilitates SPHK1 degradation via promoting K48-linked polyubiquitination. OTUB1 prohibits the TRIM21-induced ubiquitination of SPHK1 to maintain its high expression level. These findings define a new insight into the ubiquitination regulatory axis of SPHK1 and demonstrate that OTUB1-mediated SPHK1 stabilization facilitates proliferation and migration of HCC cells.

摘要

鞘氨醇激酶1（SPHK1）对于维持细胞脂质平衡至关重要。SPHK1的异常表达通过多种信号通路加剧肿瘤的恶性程度。在此，我们报道了一种关于SPHK1泛素化的新型调控机制。结果表明，TRIM21通过促进K48连接的多聚泛素化来促进SPHK1的降解。OTUB1抑制TRIM21诱导的SPHK1泛素化，以维持其高表达水平。这些发现为SPHK1泛素化调控轴提供了新的见解，并表明OTUB1介导的SPHK1稳定促进了肝癌细胞的增殖和迁移。