生物
分子生物学
细胞生长
髓系白血病
人口
程序性细胞死亡
染色体易位
细胞凋亡
抄写(语言学)
基因
转录因子
细胞生物学
遗传学
癌症研究
哲学
人口学
社会学
语言学
作者
Ricky W. Johnstone,Mark A. Gerber,Theresa Landewe,Anne Tollefson,William S.M. Wold,Ali Shilatifard
标识
DOI:10.1128/mcb.21.5.1672-1681.2001
摘要
AbstractThe ELL gene encodes an RNA polymerase II transcription factor that frequently undergoes translocation with the MLLgene in acute human myeloid leukemia. Here, we report that ELL can regulate cell proliferation and survival. In order to better understand the physiological role of the ELL protein, we have developed an ELL-inducible cell line. Cells expressing ELL were uniformly inhibited for growth by a loss of the G1 population and an increase in the G2/M population. This decrease in cell growth is followed by the condensation of chromosomal DNA, activation of caspase 3, poly(ADP ribose) polymerase cleavage, and an increase in sub-G1 population, which are all indicators of the process of programmed cell death. In support of the role of ELL in induction of cell death, expression of an ELL antisense RNA or addition of the caspase inhibitor ZVAD-fmk results in a reversal of ELL-mediated death. We have also demonstrated that the C-terminal domain of ELL, which is conserved among the ELL family of proteins that we have cloned (ELL, ELL2, and ELL3), is required for ELL's activity in the regulation of cell growth. These novel results indicate that ELL can regulate cell growth and survival and may explain how ELL translocations result in the development of human malignancies. ACKNOWLEDGMENTSWe thank Sarah Russell, Mark Smyth, and Trissa Miller for helpful discussions.This work is supported in part by a grant from the American Cancer Society (RPG-99-218-01-MGO) to A.S. A.S. is an Edward Mallinckrodt, Jr., Young Investigator. R.J. is a Wellcome Trust Senior Research Fellow.
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