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.

Cell Chemical Biology
|March 18, 2022
PubMed

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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