title: The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B.
abstract: We have shown previously that human cyclins A and B1 are localized differentially in the cell during interphase; cyclin A is nuclear and cyclin B1 is a cytoplasmic protein. To understand the basis of this difference we created deletion mutants and various chimeras between the two types of cyclin and expressed them in tissue culture cells by transient transfection. We find that the N-terminus of cyclin B1 contains a 42 amino acid region that is sufficient to retain the normally nuclear cyclin A in the cytoplasm. Conversely, deleting the cytoplasmic retention signal region from cyclin B1 causes the protein to become nuclear. Although the cytoplasmic retention signal region is outside the cyclin box, its sequence is well conserved in human cyclin B2, and is both necessary and sufficient to keep cyclin B2 in the cytoplasm. Thus we propose that the subcellular distribution of the B-type cyclins is determined primarily by a small region of the N-terminus which targets the cyclin--CDK complexes to particular structures in the cytoplasm.
authors.affiliation: Wellcome/CRC Institute, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Pines
authors.forename: T
authors.initials: T
authors.lastname: Hunter
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002451:Cell Compartmentation; D002453:Cell Cycle / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D016384:Consensus Sequence; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D016213:Cyclins; D011993:Recombinant Fusion Proteins