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Originally published In Press as doi:10.1074/jbc.M203951200 on August 15, 2002

J. Biol. Chem., Vol. 277, Issue 44, 41960-41969, November 1, 2002
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Characterization and Expression of Mammalian Cyclin B3, a Prepachytene Meiotic Cyclin*

Thomas B. NguyenDagger , Katia ManovaDagger §, Paola Capodieci§, Catherine Lindon||, Steve BottegaDagger **, Xiang-Yuan WangDagger Dagger , Jale Refik-RogersDagger , Jonathon Pines||, Debra J. WolgemuthDagger Dagger , and Andrew KoffDagger §§

From the Departments of Dagger  Molecular Biology and  Experimental Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, the || Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom, and the Dagger Dagger  Department of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, New York 10032

We report the identification and expression pattern of a full-length human cDNA and a partial mouse cDNA encoding cyclin B3. Cyclin B3 (CCNB3) is conserved from Caenorhabditis elegans to Homo sapiens and has an undefined meiotic function in female, but not male Drosophila melanogaster. We show that H. sapiens cyclin B3 interacts with cdk2, is localized to the nucleus, and is degraded during anaphase entry after the degradation of cyclin B1. Degradation is dependent on sequences conserved in a destruction box motif. Overexpression of nondegradable cyclin B3 blocks the mitotic cell cycle in late anaphase, and at higher doses it can interfere with progression through G1 and entry into S phase. H. sapiens cyclin B3 mRNA and protein are detected readily in developing germ cells in the human testis and not in any other tissue. The mouse cDNA has allowed us to further localize cyclin B3 mRNA to leptotene and zygotene spermatocytes. The expression pattern of mammalian cyclin B3 suggests that it may be important for events occurring in early meiotic prophase I.

* This work was supported in part by National Institutes of Health Grants GM52597 (to A. K.) and Medical Scientist Training Program (to T. B. N.) and by the Memorial Sloan-Kettering Core Grant CA08748.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ These authors contributed equally to this work.

** Present address: Curis Inc., Cambridge, MA 02138.

§§ Supported by a Pew scholarship in biomedical sciences and an Irma T. Hirschl scholarship. To whom correspondence should be addressed: RRL917D, Box 207, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Tel.: 212-639-2354; Fax: 646-422-2062; E-mail: a-koff@ski.mskcc.org.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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