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J. Biol. Chem., Vol. 278, Issue 50, 49806-49811, December 12, 2003

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EVI1 Promotes Cell Proliferation by Interacting with BRG1 and Blocking the Repression of BRG1 on E2F1 Activity^*

Yiqing Chi, Vitalyi Senyuk, Soumen Chakraborty, and Giuseppina Nucifora

From the Department of Pathology and The Cancer Center, University of Illinois, Chicago, Illinois 60607

EVI1 is a complex protein required for embryogenesis and inappropriately expressed in many types of human myeloid leukemia. Earlier we showed that the forced expression of EVI1 in murine hematopoietic precursor cells leads to their abnormal differentiation and increased proliferation. In this report, we show that EVI1 physically interacts with BRG1 and its functional homolog BRM in mammalian cells. We found that the C terminus of EVI1 interacts strongly with BRG1 and that the central and C-terminal regions of BRG1 are involved in EVI1-BRG1 interaction. Using reporter gene assays, we demonstrate that EVI1 activates the E2F1 promoter in NIH3T3 cells but not in BRG1-negative SW13 cells. Ectopic expression of BRG1 is able to repress the E2F1 promoter in vector-transfected SW13 cells but not in EVI1-transfected SW13 cells. Finally, we show that EVI1 up-regulates cell proliferation in BRG1-positive 32Dcl3 cells but not in BRG1-negative SW13 cells. Taken together, these data support the hypothesis that the interaction with BRG1 is important for up-regulation of cell-growth by EVI1.

Received for publication, September 2, 2003 , and in revised form, October 10, 2003.

^* This work was supported by NCI, National Institutes of Health Grants CA67189 and CA72675 (to G. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Scholar of the Leukemia and Lymphoma Society. To whom correspondence should be addressed: Dept. of Pathology and The Cancer Center, Molecular Biology Research Bldg., M/C 737, University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, IL 60607. Tel.: 312-413-4686; Fax: 312-413-0548; E-mail: nucifora{at}uic.edu.

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