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Molecular and Cellular Biology, January 1999, p. 612-622, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cyclin E2, a Novel G1 Cyclin That Binds Cdk2 and Is Aberrantly Expressed in Human Cancers

Jean M. Gudas, Marc Payton, Sushil Thukral, Eddy Chen, Michael Bass, Murray O. Robinson, and Steve Coats*

Amgen Inc., Thousand Oaks, California 91320

Received 6 July 1998/Returned for modification 17 August 1998/Accepted 5 October 1998

A novel cyclin gene was discovered by searching an expressed sequence tag database with a cyclin box profile. The human cyclin E2 gene encodes a 404-amino-acid protein that is most closely related to cyclin E. Cyclin E2 associates with Cdk2 in a functional kinase complex that is inhibited by both p27Kip1 and p21Cip1. The catalytic activity associated with cyclin E2 complexes is cell cycle regulated and peaks at the G1/S transition. Overexpression of cyclin E2 in mammalian cells accelerates G1, demonstrating that cyclin E2 may be rate limiting for G1 progression. Unlike cyclin E1, which is expressed in most proliferating normal and tumor cells, cyclin E2 levels were low to undetectable in nontransformed cells and increased significantly in tumor-derived cells. The discovery of a novel second cyclin E family member suggests that multiple unique cyclin E-CDK complexes regulate cell cycle progression.

* Corresponding author. Mailing address: Amgen Inc., One Amgen Center Dr., Mailstop 14-1-B, Thousand Oaks, CA 91320-1789. Phone: (805) 447-2962. Fax: (805) 447-1982. E-mail: scoats{at}amgen.com.

Molecular and Cellular Biology, January 1999, p. 612-622, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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