Emerging roles of the HECT-type E3 ubiquitin ligases in hematological malignancies

Abstract

Ubiquitination-mediated proteolysis or regulation of proteins, ultimately executed by E3 ubiquitin ligases, control a wide array of cellular processes, including transcription, cell cycle, autophagy and apoptotic cell death. HECT-type E3 ubiquitin ligases can be distinguished from other subfamilies of E3 ubiquitin ligases because they have a C-terminal HECT domain that directly catalyzes the covalent attachment of ubiquitin to their substrate proteins. Deregulation of HECT-type E3-mediated ubiquitination plays a prominent role in cancer development and chemoresistance. Several members of this subfamily are indeed frequently deregulated in human cancers as a result of genetic mutations and altered expression or activity. HECT-type E3s contribute to tumorigenesis by regulating the ubiquitination rate of substrates that function as either tumour suppressors or oncogenes. While the pathological roles of the HECT family members in solid tumors are quite well established, their contribution to the pathogenesis of hematological malignancies has only recently emerged. This review aims to provide a comprehensive overview of the involvement of the HECT-type E3s in leukemogenesis.

Pyroptosis-Related lncRNA Signatures Predict Prognosis and Indicate Immune Microenvironment Infiltration in Hepatocellular Carcinoma

“…In our study, the GSEA analysis showed that ubiquitin-mediated proteolysis and purine metabolism were active in the high-risk group, and fat metabolism was active in the low-risk group. Ubiquitin-mediated proteolysis carried out by the action of E3 ubiquitin ligases, regulates a series of cellular processes, including gene transcription, cell autophagy and apoptosis [37] . In another study, the authors proposed that targeted inhibition of purine metabolism can effectively inhibit HCC progression [38] .…”