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Published 9 July 2001. doi:10.1083/jcb.200102007
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© The Rockefeller University Press, 0021-9525/2001/7/85 $5.00
The Journal of Cell Biology, Volume 154, Number 1, July 9, 2001 85-94

Article

Activity of the APCCdh1 form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p



James N. Huang1,2,3, Iha Park1,2, Eric Ellingson1,2, Laurie E. Littlepage1,2 and David Pellman1,2

1 Department of Pediatric Oncology, The Dana-Farber Cancer Institute
2 Department of Pediatric Hematology, The Children's Hospital, Harvard Medical School, Boston, MA 02115
3 Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030

Address correspondence to David Pellman, Dana-Farber Cancer Institute/Harvard Medical School, Dept. of Pediatric Oncology, Rm. M612A, 44 Binney St., Boston, MA 02115. Tel.: (617) 632-4918. Fax: (617) 632-5757. E-mail: david_pellman{at}dfci.harvard.edu

Cell cycle progression is driven by waves of cyclin expression coupled with regulated protein degradation. An essential step for initiating mitosis is the inactivation of proteolysis mediated by the anaphase-promoting complex/cyclosome (APC/C) bound to its regulator Cdh1p/Hct1p. Yeast APCCdh1 was proposed previously to be inactivated at Start by G1 cyclin/cyclin-dependent kinase (CDK). Here, we demonstrate that in a normal cell cycle APCCdh1 is inactivated in a graded manner and is not extinguished until S phase. Complete inactivation of APCCdh1 requires S phase cyclins. Further, persistent APCCdh1 activity throughout G1 helps to ensure the proper timing of Cdc20p expression. This suggests that S phase cyclins have an important role in allowing the accumulation of mitotic cyclins and further suggests a regulatory loop among S phase cyclins, APCCdh1, and APCCdc20.

Key Words: cell cycle; cyclin-dependent kinases; mitosis; • S phase; ubiquitin


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