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Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia

Nature Communications, ISSN: 2041-1723, Vol: 10, Issue: 1, Page: 2691
2019
  • 101
    Citations
  • 0
    Usage
  • 159
    Captures
  • 1
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    101
  • Captures
    159
  • Mentions
    1
    • News Mentions
      1
      • 1

Most Recent News

Ro Versus Musashi: How One Molecule Can Turn Cancer Cells Back to Normal

Summary MSK researchers identified a new strategy for inhibiting RNA-binding proteins, which play a role in many cancers. Since 2012, Memorial Sloan Kettering cancer biologist

Article Description

The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08–2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI’s oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.

Bibliographic Details

Minuesa, Gerard; Albanese, Steven K; Xie, Wei; Kazansky, Yaniv; Worroll, Daniel; Chow, Arthur; Schurer, Alexandra; Park, Sun-Mi; Rotsides, Christina Z; Taggart, James; Rizzi, Andrea; Naden, Levi N; Chou, Timothy; Gourkanti, Saroj; Cappel, Daniel; Passarelli, Maria C; Fairchild, Lauren; Adura, Carolina; Glickman, J Fraser; Schulman, Jessica; Famulare, Christopher; Patel, Minal; Eibl, Joseph K; Ross, Gregory M; Bhattacharya, Shibani; Tan, Derek S; Leslie, Christina S; Beuming, Thijs; Patel, Dinshaw J; Goldgur, Yehuda; Chodera, John D; Kharas, Michael G

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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