Patched1 interacts with cyclin B1 to regulate cell cycle progression

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 ide...

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Bibliographic Details
Published in:	The EMBO journal 2001-05, Vol.20 (9), p.2214-2223
Main Authors:	Barnes, Elizabeth A., Kong, Monica, Ollendorff, Vincent, Donoghue, Daniel J
Format:	Article
Language:	eng
Subjects:	Animals basal cell carcinoma cdc2 gene Cell Cycle - drug effects Cell Cycle - physiology Cell Division - drug effects Cell Division - physiology Cell Line Cyclin B - metabolism Cyclin B1 cytoplasmic retention signal Hedgehog Proteins Humans Kidney - cytology Kidney - metabolism Life Sciences M checkpoint M-phase promoting factor Macromolecular Substances Maturation-Promoting Factor - metabolism Membrane Proteins - genetics Membrane Proteins - metabolism Membrane Proteins - pharmacology Mice nevoid basal cell carcinoma syndrome Patched Receptors Patched-1 Receptor patched1 gene Phosphorylation Precipitin Tests Protein Binding - drug effects Protein Binding - physiology Protein Structure, Tertiary - physiology Proteins - metabolism Proteins - pharmacology ptc1 gene Receptors, Cell Surface Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Trans-Activators Transfection Two-Hybrid System Techniques Xenopus
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Summary:	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 G2/M checkpoint by regulating the localization of MPF.
ISSN:	0261-4189 1460-2075 1460-2075