OTUB1 accelerates hepatocellular carcinoma by stabilizing RACK1 via its non-canonical ubiquitination

• DOI: 10.1007/s13402-023-00913-7
• Publication Date: 2024-02-05T13:02:21Z
• Authors: Liqun Peng; Tiangen Wu; Yingyi Liu; Dongli Zhao; Wenzhi He; Yufeng Yuan
• Keywords: Chromatin immunoprecipitation; Immunoprecipitation

Abstract Background Dysregulated ubiquitination modification occupies a pivotal role in hepatocellular carcinoma (HCC) tumorigenesis and progression. The ubiquitin aldehyde binding 1 (OTUB1) was aberrantly upregulated exhibited the pro-tumorigenic function HCC. However, underlying mechanisms responsible targets of OTUB1 remain unclear. Methods First, bioinformatics analysis, western blot immunohistochemistry staining were applied to analyze expression HCC specimens. Then, immunoprecipitation assay-tandem mass spectrometry (MS) combined with gene set enrichment analysis (GSEA) used explore downstream target OTUB1. Co-immunoprecipitation assays identify involved. Finally, we explored regulatory effect MAZ on through ChIP-qPCR dual-luciferase reporter assay. Results broadly elevated tissues promoted proliferation metastasis vitro vivo. receptor for activated C kinase (RACK1) performed as functional partner its hyperactivation associated aggressive development other malignant features by activating oncogenes transcription. Mechanistically, directly bound RACK1 at C-terminal domain decreased K48-linked non-canonical suppression activity, which stabilized protein levels cells. Therefore, significantly increased multiple PI3K/AKT FAK/ERK signaling RACK1-dependent manner Moreover, transcription factor identifying putative response element promoter area. Conclusions Our findings might provide new therapeutic strategy modifying MAZ-OTUB1-RACK1 axis.