Mitotic regulation of protein phosphatases by the fission yeast sds22 protein

Stone, Elisa M.; Yamano, Hiroyuki; Kinoshita, Noriyuki; Yanagida, Mitsuhiro

doi:10.1016/0960-9822(93)90140-j

Cited by 125 publications

(142 citation statements)

References 36 publications

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“…It has been shown that yeast Sds22 + activates the PP1, which in turn is involved in progression from metaphase to anaphase (Stone et al, 1993). In contrast, studies on mammalian Sds indicated that LRR peptide motifs derived from the rat Sds22 produced significant inhibition of PP1 (Dinischiotu et al, 1997).…”

Section: Discussionmentioning

confidence: 93%

“…The LRR cap was proposed to play a role in the protection of the hydrophobic core of the LRRs, required for the protein binding activity. It is also important to point out that mutational studies indicate that the LRR cap domain present in the yeast Sds22 is probably involved in nuclear targeting while the central repetitive domain interacts with PP1 (Stone et al, 1993). Nevertheless, Lesage et al showed that PP1 can be targeted independently from Sds22 (Lesage et al, 2004) and complexed to Sds22 in the nucleus (Dinischiotu et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

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Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine‐rich repeat protein of the human malaria parasite Plasmodium falciparum

Daher

Browaeys

Pierrot

et al. 2006

Molecular Microbiology

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SummaryThe protein called 'suppressor of the dis2 mutant ( sds22 + )' is an essential regulator of cell division in fission and budding yeasts, where its deletion causes mitotic arrest. Its role in cell cycle control appears to be mediated through the activation of protein phosphatase type 1 (PP1) in Schizosaccharomyces pombe . We have identified the Plasmodium falciparum Sds22 orthologue, which we designated PfLRR1 as it belongs to the leucine-rich repeat protein family. We showed by glutathione-S-transferase pull-down assay that the PfLRR1 gene product interacts with PfPP1, that the PfLRR1-PfPP1 complex is present in parasite extracts and that PfLRR1 inhibits PfPP1 activity. Functional studies in Xenopus oocytes revealed that PfLRR1 interacted with endogenous PP1 and overcame the G2/M cell cycle checkpoint by promoting progression to germinal vesicle breakdown (GVBD). Confirmatory results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies or okadaic acid. Taken together, these observations suggest that PfLRR1 can regulate the cell cycle by binding to PP1 and regulating its activity.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine‐rich repeat protein of the human malaria parasite Plasmodium falciparum

Daher

Browaeys

Pierrot

et al. 2006

Molecular Microbiology

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“…Nevertheless, the affinity of Sds22 for PP1 was significantly reduced by removal of the N terminus of Sds22. Strikingly, a similar N-terminal amputation of fission yeast Sds22 confers a temperature-sensitive mitotic defect (6), which may also correlate with compromised binding to PP1. Possibly, the N terminus of Sds22 folds into an N-terminal LRR-cap, like the one observed in the structure of Internalin B, a prokaryotic LRR protein of the Sds22-like family (38).…”

Section: Discussionmentioning

confidence: 99%

Binding of the Concave Surface of the Sds22 Superhelix to the α4/α5/α6-Triangle of Protein Phosphatase-1

Ceulemans

Vulsteke

Maeyer

et al. 2002

Journal of Biological Chemistry

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Functional studies of the protein phosphatase-1 (PP1) regulator Sds22 suggest that it is indirectly and/or directly involved in one of the most ancient functions of PP1, i.e. reversing phosphorylation by the Aurora-related protein kinases. We predict that the conserved portion of Sds22 folds into a curved superhelix and demonstrate that mutation to alanine of any of eight residues (Asp 148 Among the protein phosphatases that occur in all studied eukaryotic lineages, the Ser/Thr-specific protein phosphatases of type-1 are the best conserved, with more than 70% of their residues nearly invariant (1). This conservation extends well beyond structurally and catalytically important residues to include exposed residues involved in the binding of regulatory proteins. As a catalytic subunit, PP1 1 depends on the interaction with one or two regulatory subunits for subcellular localization, substrate specificity, and activity regulation (1, 2). Eukaryotic cells contain a large variety of regulatory subunits of PP1, which account for the diversified action of this phosphatase. We have recently proposed that PP1 acquired an essential function during early eukaryotic evolution by the development of sites for interaction with a primordial regulatory subunit(s) (1). This essential primordial function and the sequential acquirement of additional interaction sites and functions would then have impeded further mutation of the corresponding portion(s) of the surface. The phylogenetic distribution of PP1 indicates that this primordial function must have been acquired before the divergence of the extant eukaryotic lineages. One of the most ancient functions of PP1 is to dephosphorylate substrates of the Aurora-related protein kinases, and this is essential for the completion of mitosis (3). The regulatory subunit(s) associated with this function of PP1 remain unknown, but the protein Sds22 (38 kDa) has emerged as a prime candidate. First, both yeast and mammalian Sds22 have been shown to interact with PP1 and to be part of a complex with PP1 that is enriched in the nucleus (4 -7). Second, the Sds22 encoding gene was identified independently in fission and in budding yeast as an extra-copy suppressor of the temperaturesensitive mitotic arrest phenotypes that are associated with certain mutations of PP1 (4,5,8). Deletion of the Sds22-encoding gene caused a similar mitotic arrest, and this phenotype could be complemented by the overexpression of PP1 (4,5,8). Third, the conditionally lethal phenotype in budding yeast that was conferred by a loss-of-function mutation of the Aurora-related kinase Ipl1 (Ipl1-2), was largely relieved by the expression of certain temperature-sensitive mutant versions of Sds22 or PP1 (9, 10). The mutant Sds22 version that rescued the Ipl1-2 phenotype showed a decreased ability to interact with PP1. The expression of this mutant Sds22 did not affect the cellular levels of PP1 or Sds22, but drastically reduced the nuclear level of PP1 and caused a redistribution of the nuclear pool of PP1 (9).Hitherto, little ...

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“…These include proteins that target PP-1 to glycogen, myofibrils, and the nucleus. Interestingly, in S. pombe, a protein termed sds22 that is required in late mitosis has been shown to bind both the dis2 and sds21 PP-1 isoforms, to activate PP-1, and to alter its substrate specificity (46,47). The RB protein (p110 RB ), a tumor suppressor, is known to be hyperphosphorylated by cdc2, reaching a peak at mid-mitosis, and to be physically associated with PP-1 from mid-mitosis to early G 1 (21).…”

Section: Discussionmentioning

confidence: 99%

Cell cycle-dependent phosphorylation of mammalian protein phosphatase 1 by cdc2 kinase

Kwon

Lee

Choi

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

204

192

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Protein phosphatase 1 (PP-1) is known to be a critical component of eukaryotic cell cycle progression. In vitro, our previous studies showed that cdc2 kinase phosphorylates Thr-320 (T320) in PP-1, and that this leads to inhibition of enzyme activity. To examine directly the phosphorylation of PP-1 in intact mammalian cells, an antibody has been prepared that specifically recognizes PP-1C␣ phosphorylated at T320. Cell synchronization studies revealed in a variety of cell types that T320 of PP-1 was phosphorylated to high levels only during early to mid-mitosis. The phosphorylation of T320 of PP-1 was reduced by the cyclin-dependent protein kinase inhibitor, olomoucine, and increased by the PP-1͞PP-2A inhibitor, calyculin A. Immunof luorescence microscopy using phospho-T320 antibody indicated that in NIH 3T3 cells the phosphorylation of PP-1 began to increase from basal levels in prophase and to peak at metaphase. Immunostaining indicated that phospho-PP-1 was localized exclusively to nonchromosomal regions. Furthermore, in cell fractionation studies of mitotic cells, phospho-PP-1 was detectable only in the soluble fraction. These observations suggest that phosphorylation by cdc2 kinase in early to mid-mitosis and inhibition of PP-1 activity is likely to contribute to the increased state of phosphorylation of proteins that is critical to the initiation of normal cell division.Protein phosphorylation is widely recognized as the major mechanism that controls cell cycle progression. A family of cyclin-dependent protein kinases (CDKs) have been identified and found to be enzymes critical for the initiation and completion of DNA replication and cell division from yeast to mammals (1-5). The activity of CDKs is modulated through phosphorylation of their catalytic subunits and by association with activating or inhibiting proteins. For example, mitotic transition is mediated by the cdc2 kinase͞cyclin B complex, and activated cdc2 kinase has been found to drive dramatic structural reorganizations in the nuclear envelope, spindle apparatus, and chromosomal DNA by phosphorylation of a variety of substrates including histone, Eg5, lamin, vimentin, and plectin (6-12).Evidence suggests that serine͞threonine protein phosphatases function as crucial regulators of cell proliferation (4, 13-15). In particular, protein phosphatase 1 (PP-1), which is highly conserved in all eukaryotes, has been found to play a pivotal role in the cell cycle. Genetic studies have indicated that mutation of the enzyme in yeast, Aspergillus, and in Drosophila leads to a variety of defects in mitosis (16-18). Microinjection of anti-PP-1 antibody into B cells before cell division arrests cells at metaphase, whereas injection of PP-1 into anaphase cells accelerates cytokinesis (19). Expression of inhibitor-2, a specific PP-1 inhibitor, changes during the cell cycle, peaking during S phase and mitosis (20). Thus, the tightly balanced activity of CDKs and PP-1 appears to be required for normal cell division. However, the substrates that are targets f...

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Mitotic regulation of protein phosphatases by the fission yeast sds22 protein

Cited by 125 publications

References 36 publications

Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine‐rich repeat protein of the human malaria parasite Plasmodium falciparum

Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine‐rich repeat protein of the human malaria parasite Plasmodium falciparum

Binding of the Concave Surface of the Sds22 Superhelix to the α4/α5/α6-Triangle of Protein Phosphatase-1

Cell cycle-dependent phosphorylation of mammalian protein phosphatase 1 by cdc2 kinase

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