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Degradation of NSD3: What to Myc of it all?
Adam I Green1, George M Burslem2
1Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract:
Preventing uncontrolled gene expression is a powerful therapeutic strategy for the treatment of cancers. In this issue of Cell Chemical Biology, Xu et al. (2022) describe a series of proteolysis targeting chimeras that induce the degradation of NSD3 and suppress cMyc-related oncogene transcription in a model of acute myeloid leukemia.
Insights
Researchers developed novel proteolysis targeting chimeras to degrade NSD3, a key protein in cancer. This approach suppresses oncogene transcription, offering a new therapeutic strategy for acute myeloid leukemia.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Uncontrolled gene expression drives cancer development.
- Targeting oncogenes like cMyc is crucial for cancer therapy.
- Acute myeloid leukemia (AML) requires novel therapeutic strategies.
Purpose of the Study:
- To develop novel therapeutics for cancer treatment.
- To investigate the role of NSD3 in oncogene transcription.
- To suppress cMyc-related oncogene transcription in AML.
Main Methods:
- Design and synthesis of proteolysis targeting chimeras (PROTACs).
- Induction of NSD3 protein degradation.
- Assessment of cMyc-related oncogene transcription suppression.
- Utilizing a model of acute myeloid leukemia.
Main Results:
- Successfully developed PROTACs targeting NSD3.
- PROTACs induced significant degradation of NSD3 protein.
- Demonstrated suppression of cMyc-related oncogene transcription.
- Therapeutic potential shown in an AML model.
Conclusions:
- PROTACs targeting NSD3 are effective in degrading the target protein.
- This strategy suppresses oncogene transcription in AML.
- NSD3 degradation represents a promising therapeutic avenue for AML and potentially other cancers.
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