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Cyclin A Degradation Employs Preferentially Used Lysines and a Cyclin Box Function other than Cdk1 Binding
Vimal Ramachandran, Matthias Matzkies, Axel Dienemann and Frank A. Sprenger
volume 6 | issue 2
15 January 2007Pages: 171 - 181
This is an open-access article
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Cyclin A is targeted for mitotic destruction by the anaphase promoting complex/cyclosome (APC/C) and degradation proceeds even when proteolysis of other APC/C substrates are blocked by the spindle assembly checkpoint. Instead of a simple destruction box, a complex N-terminal destruction signal has been implicated in Cyclin A. We show here that Drosophila Cyclin A destruction employs both N- and C-terminal residues, which emphasize that a synergistic action by different parts of the protein facilitates recognition and degradation. The first KEN box, first D-box and an aspartic acid at position 70 are required at the N-terminus and they make additive contributions when the spindle checkpoint is active. From the C-terminal region, the cyclin box contributes. Single point mutations in these four elements abolish mitotic destruction. Additionally, eight lysines in the neighborhood of the N-terminal signals, which could serve as potential ubiquitin acceptor sites, are preferentially used for proteolysis. Mutations in these lysines and the N-terminal signals cause mitotic stability. However, mutating the lysines alone, only delays mitotic progression. Thus, presumably, lysines elsewhere in the protein are used when the preferred ones are absent and this requires the N-terminal signals. Furthermore, our results suggest that some function of the cyclin box other than Cdk1 binding promotes spindle checkpoint-independent recognition of Cyclin A by the APC/C.
Authors
Vimal Ramachandran
University of Cologne; Cologne, Germany
Matthias Matzkies
University of Cologne; Cologne, Germany
Axel Dienemann
University of Alberta; Edmonton, AB Canada
Frank A. Sprenger
University of Cologne; Cologne, Germany
This is an open-access article
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.