Cyclin-mediated export of human Orc1.
Viral cyclin/cdk6 complexes interact with and phosphorylate human Orc1, a component of the origin recognition complex (ORC) that functions in DNA replication. Here we assess the effect that viral cyclin has on the intracellular location of human Orc1, which is present in both nuclear and cytoplasmic pools. Overexpression of K cyclin or cyclin A results in Crm1-dependent export of Orc1 to the cytoplasm, and this process is dependent on the phosphorylation status of several cdk target sites in Orc1. These findings support a model where S phase promoting cyclin activity drives the export of a component of replication complexes.
Laman
H
H
Molecular Oncology Laboratory, Gene Regulation Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, United Kingdom.
Peters
G
G
Jones
N
N
D000595:Amino Acid Sequence / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D001224:Aspartic Acid / Q000235:genetics; D002451:Cell Compartmentation / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D019925:Cyclin A / Q000235:genetics; D019927:Cyclin E / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D016213:Cyclins / Q000235:genetics*; D003593:Cytoplasm / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D009154:Mutation / Q000502:physiology; D051738:Origin Recognition Complex; D010766:Phosphorylation; D021381:Protein Transport / Q000235:genetics*; D016196:S Phase / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
D000970:Antineoplastic Agents; C113028:CCNK protein, human; D019925:Cyclin A; D019927:Cyclin E; D016213:Cyclins; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; D007202:Indicators and Reagents; D008164:Luminescent Proteins; C497223:ORC1 protein, human; D051738:Origin Recognition Complex; D014764:Viral Proteins; D049452:Green Fluorescent Proteins; D001224:Aspartic Acid; D018844:Cyclin-Dependent Kinases; C038753:leptomycin B