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E3 Ligases and Deubiquitinases in Controlling High-Mobility Group Box (HMGB) Protein Functions
Elena V Chikhirzhina1, Alexey N Tomilin1, Anna S Tsimokha1
1Laboratory of Molecular Biology of Stem Cells, Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Av. 4, Saint Petersburg 194064, Russia.
International Journal of Molecular Sciences
|June 26, 2026
Summary
High-Mobility Group Box (HMGB) proteins are crucial for cellular processes and disease. E3 ubiquitin ligases and deubiquitinases regulate HMGB protein levels, impacting cellular homeostasis and disease states.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- High-Mobility Group Box (HMGB) proteins are key regulators of DNA-related cellular processes.
- HMGB protein dysregulation is implicated in malignant tumors and cardiovascular diseases.
- Maintaining cellular homeostasis requires strict control over HMGB protein levels and activity.
Purpose of the Study:
- To review the enzymes that regulate HMGB protein levels.
- To summarize the roles of E3 ubiquitin ligases and deubiquitinases in controlling HMGB protein function.
- To explore how these enzymes interact with HMGB proteins directly or through mediators.
Main Methods:
- Literature review of enzymes involved in HMGB protein regulation.
- Analysis of identified E3 ubiquitin ligases and deubiquitinases.
- Examination of proposed mechanisms of HMGB protein control.
Main Results:
- Several E3 ubiquitin ligases that promote HMGB degradation have been identified.
- Multiple deubiquitinases (DUBs) that stabilize HMGB proteins by removing ubiquitin tags have been discovered.
- These enzymes regulate HMGB functions through direct interactions or via mediator proteins.
Conclusions:
- E3 ubiquitin ligases and DUBs are critical regulators of HMGB protein homeostasis.
- Understanding these regulatory enzymes offers insights into HMGB-related diseases.
- Targeting these enzymes may provide therapeutic strategies for cancer and cardiovascular conditions.
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