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Molecular and Cellular Biology, March 2001, p. 1672-1681, Vol. 21, No. 5
The Peter MacCallum Cancer Institute, Gene
Regulation Laboratory, Cancer Immunology Division, East Melbourne, 3002 Victoria, Australia,1 and Edward A. Doisy Department of Biochemistry2 and
Department of Molecular Microbiology and
Immunology,3 St. Louis University School of
Medicine, St. Louis, Missouri 63104
Received 11 August 2000/Returned for modification 8 September
2000/Accepted 14 November 2000
The ELL gene encodes an RNA polymerase II transcription
factor that frequently undergoes translocation with the MLL
gene 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.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.5.1672-1681.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Functional Analysis of the Leukemia Protein ELL:
Evidence for a Role in the Regulation of Cell Growth and
Survival
*
Corresponding author. Mailing address: Edward A. Doisy
Department of Biochemistry, St. Louis University School of Medicine, St. Louis, MO 63104. Phone: (314) 577-8137. Fax: (314) 268-5737. E-mail: shilatia{at}slu.edu.
Molecular and Cellular Biology, March 2001, p. 1672-1681, Vol. 21, No. 5
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.5.1672-1681.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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