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Characterization of a Second Human Cyclin A That Is Highly Expressed in Testis and in Several Leukemic Cell Lines¹

Division of Hematology/Oncology, Cedars-Sinai Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90048 [R. Y., H. P. K.], and Instituto di Semeiotica Medica, Universita Cattolica del S. Cuore, Policlinico Agostino Gemelli, 00168 Rome, Italy [R. M.]

In this study, we isolated and characterized a human cyclin A-like gene that we named cyclin A1. Cyclin A1 has 48% identity with human cyclin A and is more related to the recently cloned murine cyclin A1 (84% identity). The human cyclin A1 is specifically expressed in testis and brain among all of the normal tissues that we studied by Northern blot analysis; in addition, it is expressed in several myeloid leukemia cell lines, including ML-1, U937, NB4, KG-1, and THP1. A sensitive reverse transcription-PCR-Southern blot method also detected low-level expression of this gene in many other hematopoietic and nonhematopoietic cell lines. The expression of cyclin A1 mRNA is differentiation- and cell cycle-regulated in the ML-1 cells. We raised polyclonal antibodies against a glutathione S-transferase-cyclin A1 fusion protein produced in Escherichia coli. In immunoblot analyses, the antibodies recognized the M_r 65,000 cyclin A1 protein in ML-1 cells. The anti-cyclin A1 also immunoprecipitated the M_r 65,000 cyclin A1, along with the M_r 33,000 cyclin-dependent kinase (CDK) 2 and other proteins at M_r 39,000, 42,000, 45,000, 95,000, and 110,000. In an in vitro kinase assay, the CDK2-cyclin A1 complex precipitated by anti-cyclin A1 showed kinase activities against histone H1. In a yeast two-hybrid assay, cyclin A1 can bind to CDK2 but not to CDC2, CDK4, and CDK5. We mapped the human cyclin A1 gene to chromosome 13q12.3–q13, approximately 1000 kb from the sequence-tagged site marker WI-3374.

¹ This research was supported by NIH Grants CA26038, CA70675-01, and CA42710, the Parker Hughes Trust, and the Concern Foundation. H. P. K. is a member of the University of California at Los Angeles Jonsson Cancer Center and holds the Mark Goodson Chair in Oncology Research at Cedars-Sinai Medical Center.

² To whom requests for reprints should be addressed, at Division of Hematology/Oncology, Davis Research Building, Room 5066, Cedars-Sinai Research Institute, University of California at Los Angeles School of Medicine, 8700 Beverly Boulevard, Los Angeles, CA 90048. Phone: (310) 855-7736; Fax: (310) 652-8411.

Received 9/20/96. Accepted 1/ 4/97.

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