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SUMO-Binding Entities SUBEs as Tools for the Enrichment, Isolation, Identification, and Characterization of the SUMO Proteome in Liver Cancer
Published on: November 1, 2019
Sumoylation as an Emerging Target in Therapeutics against Cancer
Sitong Liu1,2, Lichun Wang1, Dongjun Jiang1
1The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, Jilin, China
Abstract:
Sumoylation is the Post-translational modification gaining most of the research interest recently. Sumoylation is involved in various crucial functions of the cell such as regulation of cell cycle, DNA damage repair, apoptosis, etc. Oncology is advancing in radiotherapy, targeted chemotherapy, various forms of immunotherapy and targeted gene therapy. Researches are being conducted to prove its connotation with a variety of cancers and inhibitors are being developed to obstruct the fatal effect caused by misbalance of the SUMO-catalytic cycle. It has been shown that up-regulation of certain enzymes of Sumoylation correlates with cancer incidence in most of the cases. However, in some cases, down-regulation also associates with cancer invasion such as underexpression of UBC9 in initial stage breast cancer. This can aid in future study, treatment, and diagnosis of a variety of cancers including breast cancer, prostate cancer, lung adenocarcinoma, melanoma, multiple myeloma, etc. Various mechanistic assays are being developed and used to identify potential inhibitors against the dysregulated proteins of Sumoylation. This review summarizes the normal roles of the enzymes involved in the SUMOcatalytic cycle, their misbalanced regulation leading to tumorigenesis and nearly all the potent inhibitors identified to date, while after detailed studied it was observed that ML-792 could be a promising inhibitor in treating cancers by inhibiting Sumoylation enzymes.
Insights
Sumoylation, a key cellular process, is increasingly linked to cancer development. Researchers are exploring inhibitors like ML-792 to target SUMO enzymes for potential cancer therapies.
Area of Science:
- Biochemistry and Molecular Biology
- Oncology
- Cellular Biology
Background:
- Sumoylation is a critical post-translational modification regulating vital cellular functions including cell cycle, DNA repair, and apoptosis.
- Dysregulation of the SUMO-catalytic cycle is implicated in tumorigenesis, with altered enzyme activity correlating with various cancer types.
Purpose of the Study:
- To review the normal roles of SUMO-catalytic cycle enzymes.
- To elucidate the link between dysregulated sumoylation and tumorigenesis.
- To identify potent inhibitors of sumoylation enzymes for cancer treatment.
Main Methods:
- Literature review of sumoylation mechanisms and roles in cancer.
- Analysis of existing research on SUMO enzyme regulation in tumorigenesis.
- Evaluation of identified inhibitors targeting the SUMO-catalytic cycle.
Main Results:
- Up-regulation of certain sumoylation enzymes correlates with cancer incidence, while down-regulation (e.g., UBC9 in breast cancer) can also promote invasion.
- Various mechanistic assays are employed to discover inhibitors of dysregulated sumoylation proteins.
- ML-792 emerged as a promising inhibitor by targeting sumoylation enzymes.
Conclusions:
- Sumoylation pathway dysregulation is a significant factor in cancer development.
- Targeting sumoylation enzymes presents a viable therapeutic strategy for various cancers.
- ML-792 shows potential as an effective inhibitor for sumoylation-driven cancers.
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