Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Genes Dev
1998 Jul 15;1214:2131-43. doi: 10.1101/gad.12.14.2131.
Show Gene links
Show Anatomy links
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.
???displayArticle.abstract???
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.
???displayArticle.pubmedLink???
9679058 ???displayArticle.pmcLink???PMC317017 ???displayArticle.link???Genes Dev
Atherton-Fessler,
Cell cycle regulation of the p34cdc2 inhibitory kinases.
1994, Pubmed,
Xenbase
Atherton-Fessler,
Cell cycle regulation of the p34cdc2 inhibitory kinases.
1994,
Pubmed
,
Xenbase Bogerd,
Protein sequence requirements for function of the human T-cell leukemia virus type 1 Rex nuclear export signal delineated by a novel in vivo randomization-selection assay.
1996,
Pubmed Corbett,
Nucleocytoplasmic transport of macromolecules.
1997,
Pubmed Doye,
From nucleoporins to nuclear pore complexes.
1997,
Pubmed Dunphy,
The cdc25 protein contains an intrinsic phosphatase activity.
1991,
Pubmed Fischer,
The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs.
1995,
Pubmed Fornerod,
CRM1 is an export receptor for leucine-rich nuclear export signals.
1997,
Pubmed
,
Xenbase Fukuda,
CRM1 is responsible for intracellular transport mediated by the nuclear export signal.
1997,
Pubmed
,
Xenbase Gautier,
Cyclin B in Xenopus oocytes: implications for the mechanism of pre-MPF activation.
1991,
Pubmed
,
Xenbase Gautier,
cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
1991,
Pubmed
,
Xenbase Girard,
cdc25 is a nuclear protein expressed constitutively throughout the cell cycle in nontransformed mammalian cells.
1992,
Pubmed Görlich,
Isolation of a protein that is essential for the first step of nuclear protein import.
1994,
Pubmed
,
Xenbase Görlich,
Distinct functions for the two importin subunits in nuclear protein import.
1995,
Pubmed
,
Xenbase Görlich,
Nucleocytoplasmic transport.
1996,
Pubmed Görlich,
A novel class of RanGTP binding proteins.
1997,
Pubmed
,
Xenbase Heald,
Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase.
1993,
Pubmed Izumi,
Phosphorylation of Xenopus cyclins B1 and B2 is not required for cell cycle transitions.
1991,
Pubmed
,
Xenbase Izumi,
Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.
1992,
Pubmed
,
Xenbase Jackman,
Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatus.
1995,
Pubmed Kobayashi,
On the synthesis and destruction of A- and B-type cyclins during oogenesis and meiotic maturation in Xenopus laevis.
1991,
Pubmed
,
Xenbase Kornbluth,
Membrane localization of the kinase which phosphorylates p34cdc2 on threonine 14.
1994,
Pubmed
,
Xenbase Krek,
Vertebrate p34cdc2 phosphorylation site mutants: effects upon cell cycle progression in the fission yeast Schizosaccharomyces pombe.
1992,
Pubmed Kutay,
Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor.
1997,
Pubmed
,
Xenbase Li,
Requirement for phosphorylation of cyclin B1 for Xenopus oocyte maturation.
1995,
Pubmed
,
Xenbase Li,
Nuclear localization of cyclin B1 mediates its biological activity and is regulated by phosphorylation.
1997,
Pubmed
,
Xenbase Liu,
The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex.
1997,
Pubmed
,
Xenbase Lund,
Nonaqueous isolation of transcriptionally active nuclei from Xenopus oocytes.
1990,
Pubmed
,
Xenbase McGowan,
Cell cycle regulation of human WEE1.
1995,
Pubmed Meijer,
Cyclin is a component of the sea urchin egg M-phase specific histone H1 kinase.
1989,
Pubmed Meyer,
Nuclear transport of human immunodeficiency virus type 1, visna virus, and equine infectious anemia virus Rev proteins: identification of a family of transferable nuclear export signals.
1996,
Pubmed Millar,
The cdc25 M-phase inducer: an unconventional protein phosphatase.
1992,
Pubmed Millar,
p55CDC25 is a nuclear protein required for the initiation of mitosis in human cells.
1991,
Pubmed Mueller,
Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15.
1995,
Pubmed
,
Xenbase Mueller,
Cell cycle regulation of a Xenopus Wee1-like kinase.
1995,
Pubmed
,
Xenbase Murray,
Creative blocks: cell-cycle checkpoints and feedback controls.
1992,
Pubmed Neville,
The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export.
1997,
Pubmed Norbury,
Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates.
1991,
Pubmed
,
Xenbase Ossareh-Nazari,
Evidence for a role of CRM1 in signal-mediated nuclear protein export.
1997,
Pubmed Pines,
The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B.
1994,
Pubmed Pines,
Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport.
1991,
Pubmed Pollard,
A novel receptor-mediated nuclear protein import pathway.
1996,
Pubmed Radu,
Identification of a protein complex that is required for nuclear protein import and mediates docking of import substrate to distinct nucleoporins.
1995,
Pubmed
,
Xenbase Richards,
Requirement of guanosine triphosphate-bound ran for signal-mediated nuclear protein export.
1997,
Pubmed Scherf,
The human CAS protein which is homologous to the CSE1 yeast chromosome segregation gene product is associated with microtubules and mitotic spindle.
1996,
Pubmed Seki,
Chromosome condensation caused by loss of RCC1 function requires the cdc25C protein that is located in the cytoplasm.
1992,
Pubmed Solomon,
Role of phosphorylation in p34cdc2 activation: identification of an activating kinase.
1992,
Pubmed
,
Xenbase Stade,
Exportin 1 (Crm1p) is an essential nuclear export factor.
1997,
Pubmed Strausfeld,
Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein.
1991,
Pubmed Swenson,
Formation of gap junctions by expression of connexins in Xenopus oocyte pairs.
1989,
Pubmed
,
Xenbase Ullman,
Nuclear export receptors: from importin to exportin.
1997,
Pubmed Watanabe,
Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle.
1995,
Pubmed Wen,
Identification of a signal for rapid export of proteins from the nucleus.
1995,
Pubmed Wu,
Spatial organization of the Nim1-Wee1-Cdc2 mitotic control network in Schizosaccharomyces pombe.
1996,
Pubmed
