The mitotic peptidyl-prolyl isomerase, Pin1, interacts with Cdc25 and Plx1.
The cis/trans peptidyl-prolyl isomerase, Pin1, is a regulator of mitosis that is well conserved from yeast to man. Here we demonstrate that depletion of Pin1-binding proteins from Xenopus egg extracts results in hyperphosphorylation and inactivation of the key mitotic regulator, Cdc2/cyclin B. We show biochemically that this phenotype is a consequence of Pin1 interaction with critical upstream regulators of Cdc2/cyclin B, including the Cdc2-directed phosphatase, Cdc25, and its known regulator, Plx1. Although Pin1 could interact with Plx1 during interphase and mitosis, only the phosphorylated, mitotically active form of Cdc25 was able to bind Pin1, an event we have recapitulated using in vitro phosphorylated Cdc25. Taken together, these data suggest that Pin1 may modulate cell cycle control through interaction with Cdc25 and its activator, Plx1.
Crenshaw
D G
DG
Department of Pharmacology and Cancer Biology, Box 3686, Duke University Medical Center, C366 LSRC, Research Drive, Durham, NC 27710, USA.
Yang
J
J
Means
A R
AR
Kornbluth
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002457:Cell Extracts; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000502:physiology; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism* / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D020687:cdc25 Phosphatases; D000097869:Polo-Like Kinase 1
D017489:CDC28 Protein Kinase, S cerevisiae; D018797:Cell Cycle Proteins; D002457:Cell Extracts; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D029867:Xenopus Proteins; D020687:cdc25 Phosphatases; C102333:histone H1 kinase; C101085:Plk1 protein, Xenopus; D000097869:Polo-Like Kinase 1; C000606845:ESS1 protein, S cerevisiae; C000606846:PIN1 protein, human