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Molecular and Cellular Biology, September 2001, p. 6346-6357, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6346-6357.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Promotion of Cell Cycle Progression by Basic Helix-Loop-Helix E2A

Fang Zhao,1 Antonina Vilardi,2 Robert J. Neely,2 and John Kim Choi2,*

Department of Genetics1 and Department of Pathology and Laboratory Medicine,2 University of Pennsylvania, Philadelphia, Pennsylvania 19104

Received 30 April 2001/Returned for modification 4 June 2001/Accepted 19 June 2001

Normal B-cell development requires the E2A gene and its encoded transcription factors E12 and E47. Current models predict that E2A promotes cell differentiation and inhibits G1 cell cycle progression. The latter raises the conundrum of how B cells proliferate while expressing high levels of E2A protein. To study the relationship between E2A and cell proliferation, we established a tissue culture-based model in which the activity of E2A can be modulated in an inducible manner using E47R, an E47-estrogen fusion construct, and E47ERT, a dominant negative E47-estrogen fusion construct. The two constructs were subcloned into retroviral vectors and expressed in the human pre-B-cell line 697, the human myeloid progenitor cell line K562, and the murine fibroblastic cell line NIH 3T3. In both B cells and non-B cells, suppression of E2A activity by E47ERT inhibited G1 progression and was associated with decreased expression of multiple cyclins including the G1-phase cyclin D2 and cyclin D3. Consistent with these findings, E2A null mice expressed decreased levels of cyclin D2 and cyclin D3 transcripts. In complementary experiments, ectopic expression of E47R promoted G1 progression and was associated with increased levels of multiple cyclins, including cyclin D2 and cyclin D3. The induction of some cyclin transcripts occurred even in the absence of protein synthesis. We conclude that, in some cells, E2A can promote cell cycle progression, contrary to the present view that E2A inhibits G1 progression.

* Corresponding author. Mailing address: University of Pennsylvania, 413A SCL, 422 Curie Blvd., Philadelphia, PA 19104. Phone: (215) 573-6527. Fax: (215) 573-6523. E-mail: jkchoi{at}mail.med.upenn.edu.

Molecular and Cellular Biology, September 2001, p. 6346-6357, Vol. 21, No. 18
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.18.6346-6357.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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