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Vol. 13, Issue 3, 1030-1045, March 2002
Wellcome/Cancer Research U.K. (London) Institute and Department of
Zoology, University of Cambridge, Cambridge, United Kingdom CB2 1QR
Cyclins A and E and their partner cyclin-dependent kinases (Cdks)
are key regulators of DNA synthesis and of mitosis. Immunofluorescence studies have shown that both cyclins are nuclear and that a proportion of cyclin A is localized to sites of DNA replication. However, recently, both cyclin A and cyclin E have been implicated as regulators of centrosome replication, and it is unclear when and where these cyclin-Cdks can interact with cytoplasmic substrates. We have used live
cell imaging to study the behavior of cyclin/Cdk complexes. We found
that cyclin A and cyclin E are able to regulate both nuclear and
cytoplasmic events because they both shuttle between the nucleus and
the cytoplasm. However, we found that there are marked differences in
their shuttling behavior, which raises the possibility that cyclin/Cdk
function could be regulated at the level of nuclear import and export.
In the course of these experiments, we have also found that, contrary
to published results, mutations in the hydrophobic patch of cyclin A do
affect Cdk binding and nuclear import. This has implications for the
role of the hydrophobic patch as a substrate selection motif.
Corresponding author. E-mail address:
mrj{at}mole.bio.cam.ac.uk.
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