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Published 29 April 2002. doi:10.1083/jcb.200109045
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© The Rockefeller University Press, 0021-9525/2002/4/357 $5.00
The Journal of Cell Biology, Volume 157, Number 3, April 29, 2002 357-366

Article

Human Speedy

: a novel cell cycle regulator that enhances proliferation through activation of Cdk2



Lisa A. Porter, Ryan W. Dellinger, John A. Tynan, Elizabeth A. Barnes, Monica Kong, Jean-Luc Lenormand and Daniel J. Donoghue

Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093

Address correspondence to D.J. Donoghue, Department of Chemistry and Biochemistry, University of California San Diego, Urey Hall, Room 6114, 9500 Gilman Drive, La Jolla, CA 92093-0367. Tel.: (858) 534-2167. Fax: (858) 534-7481. E-mail: ddonoghue{at}ucsd.edu

The decision for a cell to self-replicate requires passage from G1 to S phase of the cell cycle and initiation of another round of DNA replication. This commitment is a critical one that is tightly regulated by many parallel pathways. Significantly, these pathways converge to result in activation of the cyclin-dependent kinase, cdk2. It is, therefore, important to understand all the mechanisms regulating cdk2 to determine the molecular basis of cell progression. Here we report the identification and characterization of a novel cell cycle gene, designated Speedy (Spy1). Spy1 is 40% homologous to the Xenopus cell cycle gene, X-Spy1. Similar to its Xenopus counterpart, human Speedy is able to induce oocyte maturation, suggesting similar biological characteristics. Spy1 mRNA is expressed in several human tissues and immortalized cell lines and is only expressed during the G1/S phase of the cell cycle. Overexpression of Spy1 protein demonstrates that Spy1 is nuclear and results in enhanced cell proliferation. In addition, flow cytometry profiles of these cells demonstrate a reduction in G1 population. Changes in cell cycle regulation can be attributed to the ability of Spy1 to bind to and prematurely activate cdk2 independent of cyclin binding. We demonstrate that Spy1-enhanced cell proliferation is dependent on cdk2 activation. Furthermore, abrogation of Spy1 expression, through the use of siRNA, demonstrates that Spy1 is an essential component of cell proliferation pathways. Hence, human Speedy is a novel cell cycle protein capable of promoting cell proliferation through the premature activation of cdk2 at the G1/S phase transition.

Key Words: Speedy; siRNA; proliferation; restriction point; G1/S


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