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Cancer Surv. 1997;29:133-50.

The anaphase promoting complex.

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Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.


We have proposed a preliminary model of how the anaphase promoting complex functions throughout the cell cycle, but despite the flurry of recent publications characterizing the APC--its components, regulation and substrate specificity--many fundamental questions remain to be answered. Firstly, the remaining components of the APC need to be identified and characterized. We do not know if all cyclosome components are conserved in all eukaryotes, or if higher eukaryotes, having a more complicated cell cycle machinery, maintain additional subunits for more sophisticated functional and regulatory control. In addition, we need to determine the identity of the various kinases and phosphatases that regulate the APC itself. The biochemistry of individual APC components is also a mystery, and a specific biochemical function has not been assigned to any known members of the complex. It is not at all clear which subunit(s) of the complex actually recognizes the E2 enzyme and which subunit(s) recognizes the cyclin destruction box. It is likely that many cyclosome substrates remain to be identified, and it will be interesting to determine whether all cyclosome substrates require a destruction box for their degradation or whether the APC recognizes other determinants of protein instability. Finally, we assume that the APC degrades mitotic cyclins in all proliferating cells, but whether it degrades unique cell cycle related substrates in specific tissues is unclear. Furthermore, nothing is known about APC function during meiosis, or whether the APC degrades other substrates that are not related to the cell cycle. This is an exciting and rapidly developing field in the exciting world of cell cycle biology. We expect that new findings will surely reveal many interesting surprises about this essential protein complex.

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