Increased HoxB4 Inhibits Apoptotic Cell Death in Pro-B Cells
Sung-Won Park1,‡, Kyung-Jong Won2,‡, Yong-Soo Lee3, Hye Sun Kim4, Yu-Kyung Kim1, Hyeon-Woo Lee4, Bokyung Kim2, Byeong Han Lee5, Jin-Hoi Kim6,†, and Dong-Ku Kim6,*
1Department of Biomedical Science, College of Life Science, CHA University, Seongnam 463-712, 2Department of Physiology and Medical Science, School of Medicine, Konkuk University, Chungju 380-701, 3Transplantation Research Center, Samsung Biomedical Research Institute, Seoul 135-710, 4Department of Pharmacology, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, 5Laboratory of Animal Research, Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, 6Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Korea
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HoxB4, a homeodomain-containing transcription factor, is involved in the expansion of hematopoietic stem cells and progenitor cells in vivo and in vitro, and plays a key role in regulating the balance between hematopoietic stem cell renewal and cell differentiation. However, the biological activity of HoxB4 in other cells has not been reported. In this study, we investigated the effect of overexpressed HoxB4 on cell survival under various conditions that induce death, using the Ba/F3 cell line. Analysis of phenotypical characteristics showed that HoxB4 overexpression in Ba/F3 cells reduced cell size, death, and proliferation rate. Moreover, the progression from early to late apoptotic stages was inhibited in Ba/F3 cells subjected to HoxB4 overexpression under removal of interleukin-3-mediated signal, leading to the induction of cell cycle arrest at the G2/M phase and attenuated cell death by Fas protein stimulation in vitro. Furthermore, apoptotic cell death induced by doxorubicin-treated G2/M phase cell-cycle arrest also decreased with HoxB4 overexpression in Ba/F3 cells. From these data, we suggest that HoxB4 may play an important role in the regulation of pro-B cell survival under various apoptotic death environments.