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C-terminal sequences direct cyclin D1-CRM1 binding.

Sharon Benzeno·J Alan Diehl
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Abstract

GSK-3beta-dependent phosphorylation of cyclin D1 at a conserved C-terminal residue, Thr-286, promotes CRM1-dependent cyclin D1 nuclear export. Herein, we have identified a short stretch of residues adjacent to Thr-286 that mediates CRM1 association and thus cyclin D1 nuclear export. We found that disruption of this hydrophobic patch, stretching from amino acids 290 to 295 within cyclin D1, results in constitutively nuclear cyclin D1-CDK4 complexes with an increased propensity to potentiate transformation of murine fibroblasts. Our data support a model wherein deregulation of cyclin D1 nuclear export might contribute to human neoplastic growth.

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Active Transport, Cell NucleusAmino Acid SequenceAnimalsCell ProliferationCyclin D1EpitopesFibroblastsHumansImmunoblottingKaryopherinsMiceMicroscopy, FluorescenceModels, BiologicalMolecular Sequence DataNIH 3T3 CellsNeoplasmsPhosphorylationProtein BindingProtein Structure, TertiaryReceptors, Cytoplasmic and NuclearThreonineTime FactorsExportin 1 ProteinJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Sharon Benzeno, J Alan Diehl. 2004-10-28. C-terminal sequences direct cyclin D1-CRM1 binding.. https://doi.org/10.1074/jbc.m411910200

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