PNUTS enhances <i>in vitro</i> chromosome decondensation in a PP1-dependent manner

Landsverk, Helga B.; Kirkhus, Marie; Bollen, Mathieu; Küntziger, Thomas; Collas, Philippe

doi:10.1042/bj20050678

Cited by 70 publications

(69 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, it has been observed in many organisms that the impairment of PP1 activity leads to a mitotic arrest (53)(54)(55)(56)(57). Further studies have shown that PP1 activity should be closely controlled to ensure correct centrosome separation and for the segregation/decondensation of chromosomes (6,58,59). In P. falciparum, although it has been shown that PP1 is essential for parasite survival and for the release of infectious merozoites (12,18,60,61), little is known about the expression of regulators of PP1 and on the nature of their exact functions.…”

Section: Discussionmentioning

confidence: 99%

“…Classical pairs of three-dimensional HNCACB, HN(CO)CACB, HNCO, HN(CA)CO, and HN(CA)N were processed using Bruker TOPSPIN 2.1 and used for the assignment of the backbone 1 H N , 15 N, and C␣ atoms, and C␤ (supplemental Table S2). The backbone assignment is not complete due to weak signals in several regions of the protein (N terminus, Lys 58 -Lys 68 and Asp 90 -Asn 103 ). For the assignment of the PfI3W45A mutant, only an additional pair of three-dimensional HNCACB and HN(CO)CACB was necessary.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Plasmodium falciparum Inhibitor-3 Homolog Increases Protein Phosphatase Type 1 Activity and Is Essential for Parasitic Survival

Fréville

Landrieu

García-Gimeno

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:Little is known about the regulators of phosphatase 1 enzyme activity in Plasmodium falciparum. Results: An activator, its binding motifs, and its nuclear location are presented. Reverse genetics show its essentiality for parasite survival. Conclusion:There is a potential link between this activator and the nuclear activity of this enzyme. Significance: This regulator is essential and can be considered as a potential drug target.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Plasmodium falciparum Inhibitor-3 Homolog Increases Protein Phosphatase Type 1 Activity and Is Essential for Parasitic Survival

Fréville

Landrieu

García-Gimeno

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…PNUTS contains several functional domains, including an N-terminal transcription elongation factor S-II (TFS2N) domain implicated in the transcriptional initiation or elongation of RNA polymerase (pol) II (19), a putative zinc finger domain, a consensus PP1-binding RVXF motif, and C-terminal RGG motifs that interact with homopolymeric RNA (17,20). PNUTS is ubiquitously expressed and tightly associates with chromatin during interphase but is excluded from chromosomes at early mitosis and is reloaded onto chromosomes during the transition from mitosis to interphase (21). PNUTS also enhances in vitro chromosome decondensation in a PP1-dependent manner.…”

Section: Protein Phosphatase 1 (Pp1)mentioning

confidence: 99%

Identification and Characterization of a Novel Human PP1 Phosphatase Complex

Lee

You²,

Dobrota

et al. 2010

Journal of Biological Chemistry

127

151

View full text Add to dashboard Cite

Mammalian Wdr82 is a regulatory component of the Setd1a and Setd1b histone H3-lysine 4 methyltransferase complexes and is implicated in the tethering of Setd1 complexes to transcriptional start sites of active genes. In the studies reported here, immunoprecipitation and mass spectrometry analyses reveal that Wdr82 additionally associates with multiple protein complexes, including an RNA polymerase II complex, four distinct histone H3-Lys 4 methyltransferase complexes, protein phosphatase 1 (PP1)-associated proteins, a chaperonin-containing Tcp1 complex, and other uncharacterized proteins. Further characterization of the PP1-associated proteins identified a stable multimeric complex composed of regulatory subunits PNUTS, Tox4, and Wdr82 and a PP1 catalytic subunit (denoted as the PTW/PP1 phosphatase complex). The PTW/ PP1 complex exhibits in vitro phosphatase activity in a PP1-dependent manner. Analysis of protein-protein interactions reveals that PNUTS mediates phosphatase complex formation by providing a binding platform to each component. The PNUTS and Tox4 subunits are predominantly associated with the PTW/PP1 phosphatase complex in HEK293 cells, and the integrity of this complex remains intact throughout cell cycle progression. Inducible expression of a PP1 interaction-defective form of PNUTS (W401A) or small interfering RNA-mediated depletion of PNUTS in HEK293 cells causes cell cycle arrest at mitotic exit and apoptotic cell death. PNUTS (W401A) shows normal association with chromosomes but causes defects in the process of chromosome decondensation at late telophase. These data reveal that mammalian Wdr82 functions in a variety of cellular processes and reveal a potential role of the PTW/PP1 phosphatase complex in the regulation of chromatin structure during the transition from mitosis into interphase. Protein phosphatase 1 (PP1)2 is a serine/threonine protein phosphatase involved in diverse cellular processes, such as transcription, replication, pre-mRNA splicing, protein synthesis, muscle contraction, carbohydrate metabolism, neuronal signaling, cell survival, and cell cycle progression (1-3). Mammals express three PP1 catalytic isoforms, PP1␣, PP1␥, and PP1␤/, which show distinct subcellular localization patterns (4, 5). PP1 catalytic isoforms do not exist freely in cells but rather associate with regulatory subunits to form distinct multimeric holoenzymes. In general, PP1 regulatory subunits function as signaling modules by regulating the enzymatic activity or targeting of catalytic subunits to specific substrates (6, 7). PP1 is involved in cell cycle progression, especially during mitosis and mitotic exit, and dysregulation of PP1 activity causes mitotic arrest or deficient cytokinesis in mammals (3,8,9). PP1 is associated with multiple mitotic structures, such as chromosomes, centrosomes, and spindles (4, 8, 10), and is implicated as a major phosphatase acting on phosphoproteins at mitotic exit (11-14). However, the specific regulatory or targeting subunits required for this activity are not well und...

show abstract

“…The PP1 catalytic subunits are highly mobile and their subcellular localization could change with the expression levels of the targeting proteins (Trinkle-Mulcahy et al, 2001;Trinkle-Mulcahy et al, 2003). One of the major nuclear targeting subunits of PP1a and PP1c is the phosphatase nuclear targeting subunit PNUTS [also known as serine/threonine-protein phosphatase 1 regulatory subunit 10 (PP1R10) and p99] that localizes to the nucleoplasm (Landsverk et al, 2005) and can be found occasionally in CBs (Moorhead et al, 2007). These data illustrate how dynamic and transient the targeting of PP1 to different specific subcellular sites could be.…”

Section: Introductionmentioning

confidence: 99%

A role for protein phosphatase PP1γ in SMN complex formation and subnuclear localization to Cajal bodies

Renvoisé

Quérol

Verrier

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

SummaryThe spinal muscular atrophy (SMA) gene product SMN forms with gem-associated protein 2-8 (Gemin2-8) and unrip (also known as STRAP) the ubiquitous survival motor neuron (SMN) complex, which is required for the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs), their nuclear import and their localization to subnuclear domain Cajal bodies (CBs). The concentration of the SMN complex and snRNPs in CBs is reduced upon SMN deficiency in SMA cells. Subcellular localization of the SMN complex is regulated in a phosphorylation-dependent manner and the precise mechanisms remain poorly understood. Using co-immunoprecipitation in HeLa cell extracts and in vitro protein binding assays, we show here that the SMN complex and its component Gemin8 interact directly with protein phosphatase PP1c. Overexpression of Gemin8 in cells increases the number of CBs and results in targeting of PP1c to CBs. Moreover, depletion of PP1c by RNA interference enhances the localization of the SMN complex and snRNPs to CBs. Consequently, the interaction between SMN and Gemin8 increases in cytoplasmic and nuclear extracts of PP1c-depleted cells. Twodimensional protein gel electrophoresis revealed that SMN is hyperphosphorylated in nuclear extracts of PP1c-depleted cells and expression of PP1c restores these isoforms. Notably, SMN deficiency in SMA leads to the aberrant subcellular localization of Gemin8 and PP1c in the atrophic skeletal muscles, suggesting that the function of PP1c is likely to be affected in disease. Our findings reveal a role of PP1c in the formation of the SMN complex and the maintenance of CB integrity. Finally, we propose Gemin8 interaction with PP1c as a target for therapeutic intervention in SMA.

show abstract

PNUTS enhances in vitro chromosome decondensation in a PP1-dependent manner

Cited by 70 publications

References 33 publications

Plasmodium falciparum Inhibitor-3 Homolog Increases Protein Phosphatase Type 1 Activity and Is Essential for Parasitic Survival

Plasmodium falciparum Inhibitor-3 Homolog Increases Protein Phosphatase Type 1 Activity and Is Essential for Parasitic Survival

Identification and Characterization of a Novel Human PP1 Phosphatase Complex

A role for protein phosphatase PP1γ in SMN complex formation and subnuclear localization to Cajal bodies

Contact Info

Product

Resources

About