title: Polo-like kinase 1-mediated phosphorylation stabilizes Pin1 by inhibiting its ubiquitination in human cells.
abstract: The Polo-like kinase 1 (Plk1) is a key regulator of mitosis. It is reported that the human peptidyl-prolyl cis/trans-isomerase Pin1 binds to Plk1 from mitotic cell extracts in vitro. Here we demonstrate that Ser-65 in Pin1 is the major site for Plk1-specific phosphorylation, and the polo-box domain of Plk1 is required for this phosphorylation. Interestingly, the phosphorylation of Pin1 by Plk1 does not affect its isomerase activity but rather is linked to its protein stability. Pin1 is ubiquitinated in HeLa S3 cells, and substitution of Glu for Ser-65 reduces the ubiquitination of Pin1. Furthermore, inhibition of Plk1 activity by expression of a dominant negative form of Plk1 or by transfection of small interfering RNA targeted to Plk1 enhances the ubiquitination of Pin1 and subsequently reduces the amount of Pin1 in human cancer cells. Since previous reports suggested that Plk1 is a substrate of Pin1, our work adds a new dimension to this interaction of two important mitotic regulators.
authors.affiliation: Department of Gynecology and Obstetrics, J. W. Goethe-University, Theodor-Stern-Kai 7, Frankfurt D-60590, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Eckerdt
authors.forename: Juping
authors.initials: J
authors.lastname: Yuan
authors.forename: Krishna
authors.initials: K
authors.lastname: Saxena
authors.forename: Bernd
authors.initials: B
authors.lastname: Martin
authors.forename: Sven
authors.initials: S
authors.lastname: Kappel
authors.forename: Christine
authors.initials: C
authors.lastname: Lindenau
authors.forename: Andrea
authors.initials: A
authors.lastname: Kramer
authors.forename: Steffen
authors.initials: S
authors.lastname: Naumann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Daum
authors.forename: Gunter
authors.initials: G
authors.lastname: Fischer
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebhardt
mesh_terms: D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007668:Kidney / Q000378:metabolism; D008938:Mitosis; D016297:Mutagenesis, Site-Directed; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D012694:Serine / Q000737:chemistry / Q000235:genetics; D025801:Ubiquitin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012694:Serine; D025801:Ubiquitin; D000097869:Polo-Like Kinase 1; C000606846:PIN1 protein, human