SAE1 promotes tumor cell malignancy via SUMOylation and liquid-liquid phase separation facilitated nuclear export of p27
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View abstract on PubMed
Summary
This summary is machine-generated.SUMOylation activating enzyme subunit 1 (SAE1) drives multiple myeloma (MM) malignancy by promoting p27 nuclear export. Colchicine targets SAE1, showing efficacy in preclinical models and a clinical trial for MM and potentially other cancers.
Area Of Science
- Oncology
- Molecular Biology
- Biochemistry
Background
- Abnormal post-translational modifications (PTMs) contribute to cancer's incurability.
- Multiple myeloma (MM) malignancy is influenced by aberrant cellular processes.
Purpose Of The Study
- To investigate the role of SUMOylation activating enzyme subunit 1 (SAE1) in multiple myeloma (MM) progression.
- To identify potential therapeutic targets and agents for MM treatment.
Main Methods
- Proteome microarray analysis to identify SAE1 targets.
- In vitro and in vivo proliferation assays.
- Crystal structure determination of SAE1 and its binding with colchicine.
- Patient-Derived Tumor Xenograft (PDX) models and clinical trials.
Main Results
- SAE1 promotes MM malignancy, with elevated levels correlating with poor survival and increased proliferation.
- SAE1 upregulates p27 expression via SUMOylation, causing p27 nuclear export and evasion of growth arrest.
- Colchicine identified as a potential inhibitor of SAE1, demonstrating efficacy in preclinical and clinical settings for MM.
Conclusions
- SAE1-mediated p27 SUMOylation and nuclear export is a novel mechanism for tumor growth evasion.
- SAE1 represents a promising therapeutic target for MM and other cancers.
- Colchicine shows potential as a clinical treatment option for various cancers.
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