The Next Frontier: Translational Development of Ubiquitination, SUMOylation, and NEDDylation in Cancer

Abstract

Post-translational modifications of proteins ensure optimized cellular processes, including proteostasis, regulated signaling, cell survival, and stress adaptation to maintain a balanced homeostatic state. Abnormal post-translational modifications are associated with cellular dysfunction and the occurrence of life-threatening diseases, such as cancer and neurodegenerative diseases. Therefore, some of the frequently seen protein modifications have been used as disease markers, while others are targeted for developing specific therapies. The ubiquitin and ubiquitin-like post-translational modifiers, namely, small ubiquitin-like modifier (SUMO) and neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8), share several features, such as protein structures, enzymatic cascades mediating the conjugation process, and targeted amino acid residues. Alterations in the regulatory mechanisms lead to aberrations in biological processes during tumorigenesis, including the regulation of tumor metabolism, immunological modulation of the tumor microenvironment, and cancer stem cell stemness, besides many more. Novel insights into ubiquitin and ubiquitin-like pathways involved in cancer biology reveal a potential interplay between ubiquitination, SUMOylation, and NEDDylation. This review outlines the current understandings of the regulatory mechanisms and assay capabilities of ubiquitination, SUMOylation, and NEDDylation. It will further highlight the role of ubiquitination, SUMOylation, and NEDDylation in tumorigenesis.

Ubiquitination, SUMOylation, and NEDDylation related genes serve as prognostic and therapeutic biomarkers for oral squamous cell carcinoma

“…The processes underpinning tumor susceptibility to UB/UBL modifications have been the focus of significant investigation in recent years, 27 GSVA studies found that crucial biological pathways and processes like MTORC1 and MYC were enriched. Yan's research found that SUMOylation of AMPK1 reduces AMPK activity primarily for mTORC1 signaling 28 .…”

MLN4924 Promotes Self-Renewal of Limbal Stem Cells and Ocular Surface Restoration

“…MLN4924 is undergoing several clinical studies to evaluate its anticancer effects on solid tumors and leukemia. Five phase I clinical trials have been completed, suggesting that MLN4924 alone or in combination with chemotherapy is safe and shows effective therapeutic effects [ 40 ]. Moreover, the potential anticancer mechanism of MLN4924 is its inhibitory effect on NAE activity by binding to NAE to produce a covalent NEDD8-MLN4924-adduct [ 41 ].…”

A New Potential Therapeutic Target for Cancer in Ubiquitin-Like Proteins—UBL3

“…This system constitutes the ubiquitin–proteasome system (UPS). UPS is the major protein hydrolysis control system in cells, which regulates the clearance of misfolded and aggregated proteins and most excess produced normal proteins [ 17 ].…”