Exp Mol Med.
2005 Dec;37(6):624-630.
Bis induces growth inhibition and differentiation of HL-60 cells via up-regulation of p27
- Affiliations
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- 1Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. leejh@catholic.ac.kr
- 2Division of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, St. Mary's Hospital, Seoul 150-713, Korea.
- 3System Proteomics Research Center, Korean Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea.
Abstract
- 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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