title: Poly(A) polymerase phosphorylation is dependent on novel interactions with cyclins.
abstract: We have previously shown that poly(A) polymerase (PAP) is negatively regulated by cyclin B-cdc2 kinase hyperphosphorylation in the M phase of the cell cycle. Here we show that cyclin B(1) binds PAP directly, and we demonstrate further that this interaction is mediated by a stretch of amino acids in PAP with homology to the cyclin recognition motif (CRM), a sequence previously shown in several cell cycle regulators to target specifically G(1)-phase-type cyclins. We find that PAP interacts with not only G(1)- but also G(2)-type cyclins via the CRM and is a substrate for phosphorylation by both types of cyclin-cdk pairs. PAP's CRM shows novel, concentration-dependent effects when introduced as an 8-mer peptide into binding and kinase assays. While higher concentrations of PAP's CRM block PAP-cyclin binding and phosphorylation, lower concentrations induce dramatic stimulation of both activities. Our data not only support the notion that PAP is directly regulated by cyclin-dependent kinases throughout the cell cycle but also introduce a novel type of CRM that functionally interacts with both G(1)- and G(2)-type cyclins in an unexpected way.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Bond
authors.forename: C
authors.initials: C
authors.lastname: Prives
authors.forename: J L
authors.initials: JL
authors.lastname: Manley
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011062:Polynucleotide Adenylyltransferase / Q000235:genetics / Q000378:metabolism*
chemical_list: D016213:Cyclins; D010446:Peptide Fragments; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases; D011062:Polynucleotide Adenylyltransferase