摘要：

The peptidyl-prolyl isomerase Pin1 interacts in a phosphorylation-dependent manner with several proteins involved in cell cycle events. In this study, we demonstrate that Pin1 interacts with protein kinase CK2, an enzyme that generally exists in tetrameric complexes composed of two catalytic CK2α and/or CK2α′ subunits together with two regulatory CK2β subunits. Our results indicate that Pin1 can interact with CK2 complexes that contain CK2α. Furthermore, Pin1 can interact directly with the C-terminal domain of CK2α that contains residues that are phosphorylated in vitro by p34 Cdc2 and in mitotic cells. Substitution of the phosphorylation sites of CK2α with alanines resulted in decreased interactions between Pin1 and CK2. The other catalytic isoform of CK2, designated CK2α′, is not phosphorylated in mitotic cells and does not interact with Pin1, but a chimeric protein consisting of CK2α′ with the C terminus of CK2α was phosphorylated in mitotic cells and interacts with Pin1, further implicating the phosphorylation sites in the interaction. In vitro , Pin1 inhibits the phosphorylation of Thr-1342 on human topoisomerase IIα by CK2. Topoisomerase IIα also interacts with Pin1 suggesting that the effect of Pin1 on the phosphorylation of Thr-1342 could result from its interactions with CK2 and/or topoisomerase IIα. As compared with wild-type Pin1, isomerase-deficient and WW domain-deficient mutants of Pin1 are impaired in their ability to interact with CK2 and to inhibit the CK2-catalyzed phosphorylation of topoisomerase IIα. Collectively, these results indicate that Pin1 and CK2α interact and suggest a possible role for Pin1 in the regulation of topoisomerase IIα. Furthermore, these results provide new insights into the functional role of the mitotic phosphorylation of CK2 and provide a new mechanism for selectively regulating the ability of CK2 to phosphorylate one of its mitotic targets.

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