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Published online 2 April 2001. doi:10.1083/jcb.153.1.137
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© The Rockefeller University Press, 0021-9525/2001//137 $5.00
The Journal of Cell Biology, Volume 153, Number 1, , 2001 137-148


Original Article

Anaphase-Promoting Complex/Cyclosome–Dependent Proteolysis of Human Cyclin a Starts at the Beginning of Mitosis and Is Not Subject to the Spindle Assembly Checkpoint



Stephan Geleya, Edgar Kramerb, Christian Gieffersb, Julian Gannona, Jan-Michael Petersb, and Tim Hunta

a Imperial Cancer Research Fund Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom
b Institute for Molecular Pathology, A-1030 Vienna, Austria
ICRF Clare Hall Labs, South Mimms, Potters Bar, Herts EN6 3LD, UK.44-20-7269-380444-20-7269-3981

tim.hunt{at}icrf.icnet.uk

Cyclin A is a stable protein in S and G2 phases, but is destabilized when cells enter mitosis and is almost completely degraded before the metaphase to anaphase transition. Microinjection of antibodies against subunits of the anaphase-promoting complex/cyclosome (APC/C) or against human Cdc20 (fizzy) arrested cells at metaphase and stabilized both cyclins A and B1. Cyclin A was efficiently polyubiquitylated by Cdc20 or Cdh1-activated APC/C in vitro, but in contrast to cyclin B1, the proteolysis of cyclin A was not delayed by the spindle assembly checkpoint. The degradation of cyclin B1 was accelerated by inhibition of the spindle assembly checkpoint. These data suggest that the APC/C is activated as cells enter mitosis and immediately targets cyclin A for degradation, whereas the spindle assembly checkpoint delays the degradation of cyclin B1 until the metaphase to anaphase transition. The "destruction box" (D-box) of cyclin A is 10–20 residues longer than that of cyclin B. Overexpression of wild-type cyclin A delayed the metaphase to anaphase transition, whereas expression of cyclin A mutants lacking a D-box arrested cells in anaphase.

Key Words: cyclin A • ubiquitin • APC/C • spindle assembly checkpoint • mitosis



© 2001 The Rockefeller University Press

The online version of this article contains supplemental material.

Abbreviations used in this paper: APC/C, anaphase-promoting complex/cyclosome; CFP, cyan fluorescent protein; CHX, cycloheximide; D-box, destruction box; GFP, green fluorescent protein; NEBD, nuclear envelope breakdown; SCF, Skp1/Cullin/F-box protein complex; YFP, yellow fluorescent protein.



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