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

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.