This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gong, J. Articles by Darzynkiewicz, Z. Search for Related Content PubMed PubMed Citation Articles by Gong, J. Articles by Darzynkiewicz, Z.

Staurosporine Blocks Cell Progression through G₁ between the Cyclin D and Cyclin E Restriction Points¹

The Cancer Research Institute, New York Medical College, Valhalla, New York 10595

The protein kinase inhibitor staurosporine (SSP) stops progression of normal nontransformed cells in the G₁ phase of the cell cycle. This implies that at least one of the cell cycle associated kinases, essential for cell transit through G₁, is sensitive to SSP. Using multivariate flow cytometry to correlate the expression of cyclin E or cyclin D with cellular DNA content (i.e., cell cycle position), we have presently characterized the point of action of SSP in relation to the expression of these cyclins. During stimulation of normal human lymphocytes by phytohemagglutinin, cyclin D was expressed early, peaking at 8–14 h, while cyclin E appeared later, reaching a maximum at the time of cell entrance to S phase (24 h). Addition of SSP at the time of cell stimulation, while markedly suppressing the expression of cyclin E, had a rather modest effect on the expression of cyclin D. The data indicate that the SSP sensitive kinase(s) involved in cell progression through G₁ operate beyond the restriction point of cyclin D but prior to that of cyclin E. Thus, the target(s) of SSP is (are) either the p33^cdk/cyclin E complex itself or other protein kinase(s), activated subsequent to the cyclin D but prior to the cyclin E restriction point, the activity of which is essential for cell transit through G₁.

¹ This work was supported by USPHS Grant CA 28704. J. G., on leave from the Department of Surgery, Tongji Hospital, Wuhan, China, was supported by a Fellowship from the "This Close" for Cancer Research Foundation.

² To whom requests for reprints should be addressed, at The Cancer Research Institute, New York Medical College, 100 Grasslands Road, Elmsford, NY 10523.

Received 4/ 8/94. Accepted 5/ 3/94.

This article has been cited by other articles:

				X. Chen, M. Lowe, T. Herliczek, M. J. Hall, C. Danes, D. A. Lawrence, and K. Keyomarsi Protection of Normal Proliferating Cells Against Chemotherapy by Staurosporine-Mediated, Selective, and Reversible G1 Arrest J Natl Cancer Inst, December 20, 2000; 92(24): 1999 - 2008. [Abstract] [Full Text] [PDF]