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<p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年8月30日

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

摘要

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.