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Myoseverin, a microtubule-binding molecule with novel cellular effects

Nature Biotechnology volume 18, pages 304–308 (2000)Cite this article

Abstract

A new microtubule-binding molecule, myoseverin, was identified from a library of 2,6,9-trisubstituted purines in a morphological differentiation screen. Myoseverin induces the reversible fission of multinucleated myotubes into mononucleated fragments. Myotube fission promotes DNA synthesis and cell proliferation after removal of the compound and transfer of the cells to fresh growth medium. Transcriptional profiling and biochemical analysis indicate that myoseverin alone does not reverse the biochemical differentiation process. Instead, myoseverin affects the expression of a variety of growth factor, immunomodulatory, extracellular matrix-remodeling, and stress response genes, consistent with the activation of pathways involved in wound healing and tissue regeneration.

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Figure 1: Myoseverin induces myotube fission.
Figure 2: Myoseverin disrupts the structure of the microtubule cytoskeleton.
Figure 3: (A) Biotinylated myoseverin affinity label.
Figure 4: Myoseverin facilitates cell cycle re-entry.

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Author notes

  1. Gustavo R. Rosania

    Present address: Cellomics, Inc., 635 William Pitt Way, Pittsburgh, PA, 15238

  2. Daniel Sutherlin

    Present address: Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080

  3. Helin Dong

    Present address: Affymetrix, Inc., 3380 Central Expressway, Santa Clara, CA, 95051

Authors and Affiliations

  1. The Scripps Research Institute, 10550 N. Torrey Pines Rd., San Diego, 92037 , CA

    Gustavo R. Rosania, Young-Tae Chang, Omar Perez, Daniel Sutherlin & Peter G. Schultz

  2. Genomics Institute of the Novartis Research Foundation , 3115 Merryfield Rd., San Diego, 92121, CA

    Helin Dong, David J. Lockhart & Peter G. Schultz

Authors
  1. Gustavo R. Rosania
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  2. Young-Tae Chang
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Correspondence to Peter G. Schultz.

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Rosania, G., Chang, YT., Perez, O. et al. Myoseverin, a microtubule-binding molecule with novel cellular effects . Nat Biotechnol 18, 304–308 (2000). https://doi.org/10.1038/73753

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