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Bis induces growth inhibition and differentiation of HL-60 cells via up-regulation of p27


Bis (Bag-3, CAIR), a Bcl-2-interacting protein, promotes the anti-apoptotic activity of Bcl-2 and increased levels of Bis have been observed in several disease models. The involvement of Bcl-2 and some Bcl-2-binding proteins in differentiation has recently been reported. However, the relevance of Bis to cellular differentiation remains unknown. The findings herein show that Bis expression is up-regulated during the differentiation of HL-60 cells. To investigate the effect of Bis expression on differentiation, we established Bis-overexpressing HL-60 cells (HL-60-bis). HL-60-bis cells have a low nuclear: cytoplasmic ratio and indented nucleus in Wright- Giemsa staining, and an increased expression of CD11b in immunofluorescence study, indicating the promotion of differentiation. The overexpression of Bis also resulted in a retarded cell growth rate, accompanied by the accumulation of HL-60 cells at the G0/G1 phase of the cell cycle, which was sustained during the differentiation process. Western blot analysis revealed that the expression of p27, a representative inducer of cell cycle arrest at the G1 phase, was increased 2.5-fold in HL-60-bis cells compared to HL-60-neo cells. These results suggest that the Bis induced growth inhibition of HL-60 cells promotes G0/G1 phase arrest via up-regulation of p27, which seems to be a prerequisite for differentiation. Further studies will be required to define the exact roles of Bis on cellular differentiation more precisely.

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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Seo, YJ., Jeon, MH., Lee, JH. et al. Bis induces growth inhibition and differentiation of HL-60 cells via up-regulation of p27. Exp Mol Med 37, 624–630 (2005).

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  • BAG3 protein, human
  • cell differentiation
  • cyclin-dependent kinase inhibitor p27
  • HL-60 cells

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