Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1.

Yang, J

Bardes, ES

Moore, JD

Brennan, J

Powers, MA

Kornbluth, S

United States

2014-03-06T17:06:29Z

1998-07-15

Activation of the Cyclin B/Cdc2 kinase complex triggers entry into mitosis in all eukaryotic cells. Cyclin B1 localization changes dramatically during the cell cycle, precipitously transiting from the cytoplasm to the nucleus at the beginning of mitosis. Presumably, this relocalization promotes the phosphorylation of nuclear targets critical for chromatin condensation and nuclear envelope breakdown. We show here that the previously characterized cytoplasmic retention sequence of Cyclin B1, responsible for its interphase cytoplasmic localization, is actually an autonomous nuclear export sequence, capable of directing nuclear export of a heterologous protein, and able to bind specifically to the recently identified export mediator, CRM1. We propose that the observed cytoplasmic localization of Cyclin B1 during interphase reflects the equilibrium between ongoing nuclear import and rapid CRM1-mediated export. In support of this hypothesis, we found that treatment of cells with leptomycin B, which disrupted Cyclin B1-CRM1 interactions, led to a marked nuclear accumulation of Cyclin B1. In mitosis, Cyclin B1 undergoes phosphorylation at several sites, a subset of which have been proposed to play a role in Cyclin B1 accumulation in the nucleus. Both CRM1 binding and the ability to direct nuclear export were affected by mutation of these phosphorylation sites; thus, we propose that Cyclin B1 phosphorylation at the G2/M transition prevents its interaction with CRM1, thereby reducing nuclear export and facilitating nuclear accumulation.

http://www.ncbi.nlm.nih.gov/pubmed/9679058

0890-9369

https://hdl.handle.net/10161/8386

eng

Cold Spring Harbor Laboratory

Genes Dev

Animals

Binding Sites

Biological Transport

Carrier Proteins

Cyclin B

Cyclin B1

Fatty Acids, Unsaturated

Guanosine Diphosphate

HeLa Cells

Humans

Intracellular Signaling Peptides and Proteins

Karyopherins

Mice

Nuclear Proteins

Phosphorylation

Rats

Receptors, Cytoplasmic and Nuclear

Recombinant Fusion Proteins

Xenopus

Xenopus laevis

ran GTP-Binding Protein

Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1.

Journal article

http://www.ncbi.nlm.nih.gov/pubmed/9679058

2131

2143

14

Basic Science Departments

Duke

Duke Cancer Institute

Institutes and Centers

Pharmacology & Cancer Biology

School of Medicine

Published

12