Rosania G R, Chang Y T, Perez O, Sutherlin D, Dong H, Lockhart D J, Schultz P G
The Scripps Research Institute, 10550 N. Torrey Pines Rd., San Diego, CA 92037, USA.
Nat Biotechnol. 2000 Mar;18(3):304-8. doi: 10.1038/73753.
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.
在一项形态分化筛选中,从一个2,6,9-三取代嘌呤文库中鉴定出一种新的微管结合分子——肌动蛋白裂解素。肌动蛋白裂解素可诱导多核肌管可逆性分裂成单核片段。去除该化合物并将细胞转移至新鲜生长培养基后,肌管分裂可促进DNA合成和细胞增殖。转录谱分析和生化分析表明,仅肌动蛋白裂解素不会逆转生化分化过程。相反,肌动蛋白裂解素会影响多种生长因子、免疫调节、细胞外基质重塑和应激反应基因的表达,这与伤口愈合和组织再生相关途径的激活一致。