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Molecular and Cellular Biology, March 2007, p. 2048-2058, Vol. 27, No. 6
0270-7306/07/$08.00+0     doi:10.1128/MCB.01100-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

c-Myb Contributes to G2/M Cell Cycle Transition in Human Hematopoietic Cells by Direct Regulation of Cyclin B1 Expression{triangledown}

Yuji Nakata, Susan Shetzline, Chizuko Sakashita, Anna Kalota, Ravikumar Rallapalli, Stephen I. Rudnick, Yi Zhang, Stephen G. Emerson, and Alan M. Gewirtz*

Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 19 June 2006/ Returned for modification 7 August 2006/ Accepted 2 January 2007

Myb family proteins are ubiquitously expressed transcription factors. In mammalian cells, they play a critical role in regulating the G1/S cell cycle transition but their role in regulating other cell cycle checkpoints is incompletely defined. Herein, we report experiments which demonstrate that c-Myb upregulates cyclin B1 expression in normal and malignant human hematopoietic cells. As a result, it contributes directly to G2/M cell cycle progression. In cell lines and primary cells, cyclin B1 levels varied directly with c-Myb expression. Chromatin immunoprecipitation assays, mutation analysis, and luciferase reporter assays revealed that c-Myb bound the cyclin B1 promoter preferentially at a site just downstream of the transcriptional start site. The biological significance of c-Myb, versus B-Myb, binding the cyclin B1 promoter was demonstrated by the fact that expression of inducible dominant negative c-Myb in K562 cells accelerated their exit from M phase. In addition, expression of c-Myb in HCT116 cells rescued cyclin B1 expression after B-myb expression was silenced with small interfering RNA. These results suggest that c-Myb protein plays a previously unappreciated role in the G2/M cell cycle transition of normal and malignant human hematopoietic cells and expands the known repertoire of c-myb functions in regulating human hematopoiesis.

* Corresponding author. Mailing address: Division of Hematology/Oncology, Department of Medicine, Room 713, BRB II/III, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104. Phone: (215) 898-4499. Fax: (215) 573-7049. E-mail: gewirtz{at}mail.med.upenn.edu.

{triangledown} Published ahead of print on 22 January 2007.

Molecular and Cellular Biology, March 2007, p. 2048-2058, Vol. 27, No. 6
0270-7306/07/$08.00+0     doi:10.1128/MCB.01100-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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