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The cdc2-related Kinase, PISSLRE, Is Essential for Cell Growth and Acts in G₂ Phase of the Cell Cycle¹

Jefferson Cancer Institute and Departments of Microbiology and Immunology and Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Mammalian cell cycle progression is regulated by several protein kinases that are activated by cyclically expressed proteins called cyclins. These cyclin-dependent kinases, the prototype of which is the cdc2 mitosis-promoting kinase, are known to phosphorylate substrates the modified status of which is critical for the cell to progress into sequential phases of the cycle. Recently, a new cdc2-related protein kinase has been discovered, PISSLRE, named with respect to its homology to the cdc2 PSTAIRE amino acid domain. Here we report that by using both antisense and dominant-negative mutant constructs of PISSLRE when overexpressed in U2OS cells, a growth suppression is found. Furthermore, the dominant negative forms of PISSLRE halt cell cycle progression in G₂-M. Therefore, PISSLRE is essential for cellular proliferation, and its effect is exerted in G₂-M. This describes the first evidence since cdc2 of a cdc2-related kinase acting through G₂-M.

¹ T. K. M. is supported by NIH Training Grant 1-T32-HL07780; A. D. L. is supported by a fellowship from Universita' di Bari (Dottorato di Ricerca in Morfologia Umana e Sperimentale); P. P. C. is on leave of absence from the Dipartimento di Chirurgia Maxillo-Faciale, Facolta' di Medicina, Universita' di Napoli, "Federico II," Italy and is supported by a fellowship from the American-Italian Cancer Foundation. This work was supported by the Sbarro Institute for Cancer Research and Molecular Medicine, NIH Grant RO1 CA60999-01A1, and the Council for Tobacco Research.

² To whom requests for reprints should be addressed, at Sbarro Institute for Cancer Research and Molecular Medicine, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107. Telephone: (215) 955-4614; FAX: (215) 923-9626.

Received 7/19/95. Accepted 8/ 4/95.

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