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Molecular and Cellular Biology, March 1999, p. 2400-2407, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Functions of Cyclin A1 in the Cell Cycle and Its Interactions with Transcription Factor E2F-1 and the Rb Family of Proteins

Rong Yang,1,* Carsten Müller,1 Vong Huynh,1 Yuen K. Fung,2 Amy S. Yee,3 and H. Phillip Koeffler1

Division of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, California 900481; Division of Hematology/Oncology, USC School of Medicine, Childrens Hospital Los Angeles, Los Angeles, California 900272; and Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 021113

Received 27 March 1998/Returned for modification 13 May 1998/Accepted 19 November 1998

Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.

* Corresponding author. Mailing address: Division of Hematology/Oncology, Davis Research Building, Rm. 5066, Cedars-Sinai Research Institute, UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048. Phone: (310) 855-7736. Fax: (310) 652-8411. E-mail: yangr{at}CSMC.edu.

Molecular and Cellular Biology, March 1999, p. 2400-2407, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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