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Molecular and Cellular Biology, December 1998, p. 7584-7589, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Maturation of Human Cyclin E Requires the Function of Eukaryotic Chaperonin CCT

Kwang-Ai Won,1 Robert J. Schumacher,2 George W. Farr,2 Arthur L. Horwich,2 and Steven I. Reed1,*

Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037,1 and Department of Genetics and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 065102

Received 10 June 1998/Returned for modification 13 August 1998/Accepted 21 August 1998

Cyclin E, a partner of the cyclin-dependent kinase Cdk2, has been implicated in positive control of the G1/S phase transition. Whereas degradation of cyclin E has been shown to be exquisitely regulated by ubiquitination and proteasomal action, little is known about posttranscriptional aspects of its biogenesis. In a yeast-based screen designed to identify human proteins that interact with human cyclin E, we identified components of the eukaryotic cytosolic chaperonin CCT. We found that the endogenous CCT complex in yeast was essential for the maturation of cyclin E in vivo. Under conditions of impaired CCT function, cyclin E failed to accumulate. Furthermore, newly translated cyclin E, both in vitro in reticulocyte lysate and in vivo in human cells in culture, is efficiently bound and processed by the CCT. In vitro, in the presence of ATP, the bound protein is folded and released in order to become associated with Cdk2. Thus, both the acquisition of the native state and turnover of cyclin E involve ATP-dependent processes mediated by large oligomeric assemblies.

* Corresponding author. Mailing address: Department of Molecular Biology, MB7, Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-9836. Fax: (619) 784-2781. E-mail: sreed{at}scripps.edu.

Molecular and Cellular Biology, December 1998, p. 7584-7589, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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