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EMBO J
2001 May 01;209:2214-23. doi: 10.1093/emboj/20.9.2214.
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Patched1 interacts with cyclin B1 to regulate cell cycle progression.
Barnes EA, Kong M, Ollendorff V, Donoghue DJ.
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The initiation of mitosis requires the activation of M-phase promoting factor (MPF). MPF activation and its subcellular localization are dependent on the phosphorylation state of its components, cdc2 and cyclin B1. In a two-hybrid screen using a bait protein to mimic phosphorylated cyclin B1, we identified a novel interaction between cyclin B1 and patched1 (ptc1), a tumor suppressor associated with basal cell carcinoma (BCC). Ptc1 interacted specifically with constitutively phosphorylated cyclin B1 derivatives and was able to alter their normal subcellular localization. Furthermore, addition of the ptc1 ligand, sonic hedgehog (shh), disrupts this interaction and allows cyclin B1 to localize to the nucleus. Expression of ptc1 in 293T cells was inhibitory to cell proliferation; this inhibition could be relieved by coexpression of a cyclin B1 derivative that constitutively localizes to the nucleus and that could not interact with ptc1 due to phosphorylation-site mutations to ALA: In addition, we demonstrate that endogenous ptc1 and endogenous cyclin B1 interact in vivo. The findings reported here demonstrate that ptc1 participates in determining the subcellular localization of cyclin B1 and suggest a link between the tumor suppressor activity of ptc1 and the regulation of cell division. Thus, we propose that ptc1 participates in a G(2)/M checkpoint by regulating the localization of MPF.
Borgne,
Sequential dephosphorylation of p34(cdc2) on Thr-14 and Tyr-15 at the prophase/metaphase transition.
1996, Pubmed
Borgne,
Sequential dephosphorylation of p34(cdc2) on Thr-14 and Tyr-15 at the prophase/metaphase transition.
1996,
Pubmed Borgne,
Intra-M phase-promoting factor phosphorylation of cyclin B at the prophase/metaphase transition.
1999,
Pubmed
,
Xenbase Carpenter,
Characterization of two patched receptors for the vertebrate hedgehog protein family.
1998,
Pubmed Chen,
Dual roles for patched in sequestering and transducing Hedgehog.
1996,
Pubmed Chidambaram,
Mutations in the human homologue of the Drosophila patched gene in Caucasian and African-American nevoid basal cell carcinoma syndrome patients.
1996,
Pubmed Dean,
Towards a unified model of tumor suppression: lessons learned from the human patched gene.
1997,
Pubmed Denef,
Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened.
2000,
Pubmed Ducommun,
cdc2 phosphorylation is required for its interaction with cyclin.
1991,
Pubmed
,
Xenbase Gailani,
The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas.
1996,
Pubmed Gailani,
Developmental genes and cancer: role of patched in basal cell carcinoma of the skin.
1997,
Pubmed Goodrich,
Hedgehog and patched in neural development and disease.
1998,
Pubmed Goodrich,
Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog.
1996,
Pubmed Gorlin,
Nevoid basal cell carcinoma syndrome.
1995,
Pubmed Greenwood,
Localization and in situ phosphorylation state of nuclear tau.
1995,
Pubmed Hagting,
MPF localization is controlled by nuclear export.
1998,
Pubmed Hagting,
Translocation of cyclin B1 to the nucleus at prophase requires a phosphorylation-dependent nuclear import signal.
1999,
Pubmed Hahn,
Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome.
1996,
Pubmed Hahn,
A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities.
1996,
Pubmed Incardona,
Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1.
2000,
Pubmed Jin,
Nuclear localization of cyclin B1 controls mitotic entry after DNA damage.
1998,
Pubmed Johnson,
Human homolog of patched, a candidate gene for the basal cell nevus syndrome.
1996,
Pubmed Kong,
Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin-cyclin interaction.
2000,
Pubmed
,
Xenbase Kreis,
Oligomerization is essential for transport of vesicular stomatitis viral glycoprotein to the cell surface.
1986,
Pubmed Krek,
Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites.
1991,
Pubmed Lee,
Autoproteolysis in hedgehog protein biogenesis.
1994,
Pubmed Li,
Nuclear localization of cyclin B1 mediates its biological activity and is regulated by phosphorylation.
1997,
Pubmed
,
Xenbase Li,
Requirement for phosphorylation of cyclin B1 for Xenopus oocyte maturation.
1995,
Pubmed
,
Xenbase Marigo,
Biochemical evidence that patched is the Hedgehog receptor.
1996,
Pubmed
,
Xenbase Murone,
Sonic hedgehog signaling by the patched-smoothened receptor complex.
1999,
Pubmed Murray,
The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
1989,
Pubmed
,
Xenbase Norbury,
Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates.
1991,
Pubmed
,
Xenbase Peter,
In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase.
1990,
Pubmed Pines,
The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B.
1994,
Pubmed Pondaven,
Activation of M-phase-specific histone H1 kinase by modification of the phosphorylation of its p34cdc2 and cyclin components.
1990,
Pubmed Solomon,
Cyclin activation of p34cdc2.
1990,
Pubmed
,
Xenbase Stone,
The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.
1996,
Pubmed Toyoshima,
Nuclear export of cyclin B1 and its possible role in the DNA damage-induced G2 checkpoint.
1998,
Pubmed Unden,
Mutations in the human homologue of Drosophila patched (PTCH) in basal cell carcinomas and the Gorlin syndrome: different in vivo mechanisms of PTCH inactivation.
1996,
Pubmed Undén,
Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma.
1997,
Pubmed Verde,
Control of microtubule dynamics and length by cyclin A- and cyclin B-dependent kinases in Xenopus egg extracts.
1992,
Pubmed
,
Xenbase Vojtek,
Mammalian Ras interacts directly with the serine/threonine kinase Raf.
1993,
Pubmed Vojtek,
Ras-Raf interaction: two-hybrid analysis.
1995,
Pubmed Weinberg,
The retinoblastoma protein and cell cycle control.
1995,
Pubmed Yamashiro,
Phosphorylation of non-muscle caldesmon by p34cdc2 kinase during mitosis.
1991,
Pubmed Yang,
Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1.
1998,
Pubmed
,
Xenbase Yang,
All aboard the cyclin train: subcellular trafficking of cyclins and their CDK partners.
1999,
Pubmed
