Poly(A) polymerase phosphorylation is dependent on novel interactions with cyclins.

Journal article

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: Bond, G; Prives, C; Manley, J

• Publication status: Published
• Journal: Molecular and cellular biology
• Volume: 20
• Issue: 14
• Pages: 5310-5320
• Publication date: 2000-07-01
• DOI: 10.1128/mcb.20.14.5310-5320.2000
• EISSN: 1098-5549
• ISSN: 0270-7306
• Language: English
• Keywords: Animals; G2 Phase; Cyclin-Dependent Kinases; Cells, Cultured; Polynucleotide Adenylyltransferase; CDC2 Protein Kinase; Phosphorylation; Peptide Fragments; Amino Acid Motifs; G1 Phase; Cyclins