Nuclear import of Cdk/cyclin complexes: identification of distinct mechanisms for import of Cdk2/cyclin E and Cdc2/cyclin B1.

Moore, JD

Yang, J

Truant, R

Kornbluth, S

United States

2014-03-06T15:54:17Z

1999-01-25

Reversible phosphorylation of nuclear proteins is required for both DNA replication and entry into mitosis. Consequently, most cyclin-dependent kinase (Cdk)/cyclin complexes are localized to the nucleus when active. Although our understanding of nuclear transport processes has been greatly enhanced by the recent identification of nuclear targeting sequences and soluble nuclear import factors with which they interact, the mechanisms used to target Cdk/cyclin complexes to the nucleus remain obscure; this is in part because these proteins lack obvious nuclear localization sequences. To elucidate the molecular mechanisms responsible for Cdk/cyclin transport, we examined nuclear import of fluorescent Cdk2/cyclin E and Cdc2/cyclin B1 complexes in digitonin-permeabilized mammalian cells and also examined potential physical interactions between these Cdks, cyclins, and soluble import factors. We found that the nuclear import machinery recognizes these Cdk/cyclin complexes through direct interactions with the cyclin component. Surprisingly, cyclins E and B1 are imported into nuclei via distinct mechanisms. Cyclin E behaves like a classical basic nuclear localization sequence-containing protein, binding to the alpha adaptor subunit of the importin-alpha/beta heterodimer. In contrast, cyclin B1 is imported via a direct interaction with a site in the NH2 terminus of importin-beta that is distinct from that used to bind importin-alpha.

http://www.ncbi.nlm.nih.gov/pubmed/9922449

0021-9525

https://hdl.handle.net/10161/8377

eng

Rockefeller University Press

J Cell Biol

Animals

Binding Sites

Biological Transport

CDC2 Protein Kinase

CDC2-CDC28 Kinases

Cell Nucleus

Cyclin B

Cyclin B1

Cyclin E

Cyclin-Dependent Kinase 2

Cyclin-Dependent Kinases

Humans

Karyopherins

Nuclear Proteins

Peptides

Protein-Serine-Threonine Kinases

Recombinant Fusion Proteins

Xenopus

Xenopus Proteins

Nuclear import of Cdk/cyclin complexes: identification of distinct mechanisms for import of Cdk2/cyclin E and Cdc2/cyclin B1.

Journal article

http://www.ncbi.nlm.nih.gov/pubmed/9922449

213

224

2

Basic Science Departments

Duke

Duke Cancer Institute

Institutes and Centers

Pharmacology & Cancer Biology

School of Medicine

Published

144