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Genes Dev
1998 Mar 01;125:706-20. doi: 10.1101/gad.12.5.706.
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The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins.
Shen M
,
Stukenberg PT
,
Kirschner MW
,
Lu KP
.
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Phosphorylation of mitotic proteins on the Ser/Thr-Pro motifs has been shown to play an important role in regulating mitotic progression. Pin1 is a novel essential peptidyl-prolyl isomerase (PPIase) that inhibits entry into mitosis and is also required for proper progression through mitosis, but its substrate(s) and function(s) remain to be determined. Here we report that in both human cells and Xenopus extracts, Pin1 interacts directly with a subset of mitotic phosphoproteins on phosphorylated Ser/Thr-Pro motifs in a phosphorylation-dependent and mitosis-specific manner. Many of these Pin1-binding proteins are also recognized by the monoclonal antibody MPM-2, and they include the important mitotic regulators Cdc25, Myt1, Wee1, Plk1, and Cdc27. The importance of this Pin1 interaction was tested by constructing two Pin1 active site point mutants that fail to bind a phosphorylated Ser/Thr-Pro motif in mitotic phosphoproteins. Wild-type, but not mutant, Pin1 inhibits both mitotic division in Xenopus embryos and entry into mitosis in Xenopus extracts. We have examined the interaction between Pin1 and Cdc25 in detail. Pin1 not only binds the mitotic form of Cdc25 on the phosphorylation sites important for its activity in vitro and in vivo, but it also inhibits its activity, offering one explanation for the ability of Pin1 to inhibit mitotic entry. In a separate paper, we have shown that Pin1 is a phosphorylation-dependent PPIase that can recognize specifically the phosphorylated Ser/Thr-Pro bonds present in mitotic phosphoproteins. Thus, Pin1 likely acts as a general regulator of mitotic proteins that have been phosphorylated by Cdc2 and other mitotic kinases.
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9499405
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Bailly,
Phosphorylation of two small GTP-binding proteins of the Rab family by p34cdc2.
1991, Pubmed
Bailly,
Phosphorylation of two small GTP-binding proteins of the Rab family by p34cdc2.
1991,
Pubmed
Blangy,
Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo.
1995,
Pubmed
,
Xenbase
Booher,
Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity.
1997,
Pubmed
,
Xenbase
Coleman,
Cdc2 regulatory factors.
1994,
Pubmed
Coleman,
Negative regulation of the wee1 protein kinase by direct action of the nim1/cdr1 mitotic inducer.
1993,
Pubmed
Davis,
Monoclonal antibodies to mitotic cells.
1983,
Pubmed
,
Xenbase
Davis,
Mitosis-specific monoclonal antibodies block cleavage in amphibian embryos.
1989,
Pubmed
,
Xenbase
Golsteyn,
Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function.
1995,
Pubmed
Hamanaka,
Polo-like kinase is a cell cycle-regulated kinase activated during mitosis.
1995,
Pubmed
Hanes,
Sequence and mutational analysis of ESS1, a gene essential for growth in Saccharomyces cerevisiae.
1989,
Pubmed
Heald,
Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis.
1990,
Pubmed
Hecht,
Conditional absence of mitosis-specific antigens in a temperature-sensitive embryonic-arrest mutant of Caenorhabditis elegans.
1987,
Pubmed
Heintz,
Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle.
1983,
Pubmed
Hirano,
Cell cycle control of higher-order chromatin assembly around naked DNA in vitro.
1991,
Pubmed
,
Xenbase
Izumi,
Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its activity.
1992,
Pubmed
,
Xenbase
Izumi,
Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase.
1993,
Pubmed
,
Xenbase
Johnson,
Mammalian cell fusion: induction of premature chromosome condensation in interphase nuclei.
1970,
Pubmed
Keryer,
Protein phosphorylation and dynamics of cytoskeletal structures associated with basal bodies in Paramecium.
1987,
Pubmed
King,
A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
1995,
Pubmed
,
Xenbase
King,
Mitosis in transition.
1994,
Pubmed
Krek,
Mutations of p34cdc2 phosphorylation sites induce premature mitotic events in HeLa cells: evidence for a double block to p34cdc2 kinase activation in vertebrates.
1991,
Pubmed
Kuang,
Mitosis-specific monoclonal antibody MPM-2 inhibits Xenopus oocyte maturation and depletes maturation-promoting activity.
1989,
Pubmed
,
Xenbase
Kuang,
At least two kinases phosphorylate the MPM-2 epitope during Xenopus oocyte maturation.
1993,
Pubmed
,
Xenbase
Kuang,
cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor.
1994,
Pubmed
,
Xenbase
Kumagai,
Purification and molecular cloning of Plx1, a Cdc25-regulatory kinase from Xenopus egg extracts.
1996,
Pubmed
,
Xenbase
Lee,
Inhibition of cdc2 activation by INH/PP2A.
1994,
Pubmed
,
Xenbase
Lu,
Properties and regulation of the cell cycle-specific NIMA protein kinase of Aspergillus nidulans.
1993,
Pubmed
Lu,
Evidence for a NIMA-like mitotic pathway in vertebrate cells.
1995,
Pubmed
,
Xenbase
Lu,
A human peptidyl-prolyl isomerase essential for regulation of mitosis.
1996,
Pubmed
Maleszka,
The Drosophila melanogaster dodo (dod) gene, conserved in humans, is functionally interchangeable with the ESS1 cell division gene of Saccharomyces cerevisiae.
1996,
Pubmed
Matsumoto-Taniura,
Identification of novel M phase phosphoproteins by expression cloning.
1996,
Pubmed
Mueller,
Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15.
1995,
Pubmed
,
Xenbase
Murray,
Cell cycle extracts.
1991,
Pubmed
Muslin,
Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine.
1996,
Pubmed
,
Xenbase
Nigg,
Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle.
1995,
Pubmed
Nurse,
Ordering S phase and M phase in the cell cycle.
1994,
Pubmed
Ogg,
Purification of a serine kinase that associates with and phosphorylates human Cdc25C on serine 216.
1994,
Pubmed
Pawson,
Protein modules and signalling networks.
1995,
Pubmed
Pines,
Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport.
1991,
Pubmed
Poon,
Redistribution of the CDK inhibitor p27 between different cyclin.CDK complexes in the mouse fibroblast cell cycle and in cells arrested with lovastatin or ultraviolet irradiation.
1995,
Pubmed
Ranganathan,
Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent.
1997,
Pubmed
Renzi,
MPM-2 antibody-reactive phosphorylations can be created in detergent-extracted cells by kinetochore-bound and soluble kinases.
1997,
Pubmed
Reynisdóttir,
The subcellular locations of p15(Ink4b) and p27(Kip1) coordinate their inhibitory interactions with cdk4 and cdk2.
1997,
Pubmed
Russell,
cdc25+ functions as an inducer in the mitotic control of fission yeast.
1986,
Pubmed
Schmid,
Protein folding. Prolyl isomerases join the fold.
1995,
Pubmed
Schreiber,
Chemistry and biology of the immunophilins and their immunosuppressive ligands.
1991,
Pubmed
Solomon,
Cyclin activation of p34cdc2.
1990,
Pubmed
,
Xenbase
Strausfeld,
Activation of p34cdc2 protein kinase by microinjection of human cdc25C into mammalian cells. Requirement for prior phosphorylation of cdc25C by p34cdc2 on sites phosphorylated at mitosis.
1994,
Pubmed
Stukenberg,
Systematic identification of mitotic phosphoproteins.
1997,
Pubmed
,
Xenbase
Taagepera,
The MPM-2 antibody inhibits mitogen-activated protein kinase activity by binding to an epitope containing phosphothreonine-183.
1994,
Pubmed
,
Xenbase
Taagepera,
DNA topoisomerase II alpha is the major chromosome protein recognized by the mitotic phosphoprotein antibody MPM-2.
1993,
Pubmed
Vandre,
Phosphoproteins are components of mitotic microtubule organizing centers.
1984,
Pubmed
Vandré,
Distribution of cytoskeletal proteins sharing a conserved phosphorylated epitope.
1986,
Pubmed
Vandré,
Proteins of the mammalian mitotic spindle: phosphorylation/dephosphorylation of MAP-4 during mitosis.
1991,
Pubmed
Westendorf,
Cloning of cDNAs for M-phase phosphoproteins recognized by the MPM2 monoclonal antibody and determination of the phosphorylated epitope.
1994,
Pubmed
Wordeman,
Distribution of phosphorylated spindle-associated proteins in the diatom Stephanopyxis turris.
1989,
Pubmed
Yaffe,
Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism.
1997,
Pubmed
Ye,
The NIMA protein kinase is hyperphosphorylated and activated downstream of p34cdc2/cyclin B: coordination of two mitosis promoting kinases.
1995,
Pubmed
Yu,
Identification of a cullin homology region in a subunit of the anaphase-promoting complex.
1998,
Pubmed
