scholarly journals Protein phosphatase 2A is a negative regulator of IL-2 production in patients with systemic lupus erythematosus

2005 ◽  
Vol 115 (11) ◽  
pp. 3193-3204 ◽  
Author(s):  
C. G. Katsiari
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Negative Regulator ◽  
Systemic Lupus ◽  
Phosphatase 2A

scholarly journals Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus

2019 ◽  
Vol 78 (10) ◽  
pp. 1363-1370 ◽  
Author(s):  
Lina Odqvist ◽  
Zala Jevnikar ◽  
Rebecca Riise ◽  
Lisa Öberg ◽  
Magdalena Rhedin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Genetic Alterations ◽  
Genetic Variations ◽  
Negative Regulator ◽  
Systemic Lupus ◽  
Trap Formation ◽  
Autoimmune Pathology ◽  
Extracellular Trap

ObjectivesGenetic variations in TNFAIP3 (A20) de-ubiquitinase (DUB) domain increase the risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis. A20 is a negative regulator of NF-κB but the role of its DUB domain and related genetic variants remain unclear. We aimed to study the functional effects of A20 DUB-domain alterations in immune cells and understand its link to SLE pathogenesis.MethodsCRISPR/Cas9 was used to generate human U937 monocytes with A20 DUB-inactivating C103A knock-in (KI) mutation. Whole genome RNA-sequencing was used to identify differentially expressed genes between WT and C103A KI cells. Functional studies were performed in A20 C103A U937 cells and in immune cells from A20 C103A mice and genotyped healthy individuals with A20 DUB polymorphism rs2230926. Neutrophil extracellular trap (NET) formation was addressed ex vivo in neutrophils from A20 C103A mice and SLE-patients with rs2230926.ResultsGenetic disruption of A20 DUB domain in human and murine myeloid cells did not give rise to enhanced NF-κB signalling. Instead, cells with C103A mutation or rs2230926 polymorphism presented an upregulated expression of PADI4, an enzyme regulating protein citrullination and NET formation, two key mechanisms in autoimmune pathology. A20 C103A cells exhibited enhanced protein citrullination and extracellular trap formation, which could be suppressed by selective PAD4 inhibition. Moreover, SLE-patients with rs2230926 showed increased NETs and increased frequency of autoantibodies to citrullinated epitopes.ConclusionsWe propose that genetic alterations disrupting the A20 DUB domain mediate increased susceptibility to SLE through the upregulation of PADI4 with resultant protein citrullination and extracellular trap formation.

scholarly journals Suppression of Scant Identifies Endos as a Substrate of Greatwall Kinase and a Negative Regulator of Protein Phosphatase 2A in Mitosis

PLoS Genetics ◽  
2011 ◽  
Vol 7 (8) ◽  
pp. e1002225 ◽  
Author(s):  
Hélène Rangone ◽  
Eva Wegel ◽  
Melanie K. Gatt ◽  
Eirene Yeung ◽  
Alexander Flowers ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Negative Regulator ◽  
Phosphatase 2A ◽  
Greatwall Kinase

scholarly journals TANK prevents IFN-dependent fatal diffuse alveolar hemorrhage by suppressing DNA-cGAS aggregation

2021 ◽  
Vol 5 (2) ◽  
pp. e202101067
Author(s):  
Atsuko Wakabayashi ◽  
Masanori Yoshinaga ◽  
Osamu Takeuchi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Critical Role ◽  
Vascular Endothelial Cell ◽  
Diffuse Alveolar Hemorrhage ◽  
Negative Regulator ◽  
Alveolar Hemorrhage ◽  
Type I ◽  
Systemic Lupus ◽  
Cytoplasmic Dna

Diffuse alveolar hemorrhage (DAH) is one of the serious complications associated with systemic lupus erythematosus, an autoimmune disease whose pathogenesis involves type I IFNs and cytokines. Here, we show that TANK, a negative regulator of the NF-κB signaling via suppression of TRAF6 ubiquitination, is critical for the amelioration of fatal DAH caused by lung vascular endothelial cell death in a mouse model of systemic lupus erythematosus. The development of fatal DAH in the absence of TANK is mediated by type I IFN signaling, but not IL-6. We further uncover that STING, an adaptor essential for the signaling of cytoplasmic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS), plays a critical role in DAH under Tank deficiency. TANK controls cGAS-mediated cGAMP production and suppresses DNA-mediated induction of IFN-stimulated genes in macrophages by inhibiting the formation of DNA-cGAS aggregates containing ubiquitin. Collectively, TANK inhibits the cGAS-dependent recognition of cytoplasmic DNA to prevent fatal DAH in the murine lupus model.

INH, a negative regulator of MPF, is a form of protein phosphatase 2A

Cell ◽  
1991 ◽  
Vol 64 (2) ◽  
pp. 415-423 ◽  
Author(s):  
Tina H Lee ◽  
Mark J Solomon ◽  
Marc C Mumby ◽  
Marc W Kirschner
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Negative Regulator ◽  
Phosphatase 2A

scholarly journals Protein Phosphatase 2A (PP2A) Regulatory Subunits ParA and PabA Orchestrate Septation and Conidiation and Are Essential for PP2A Activity in Aspergillus nidulans

2014 ◽  
Vol 13 (12) ◽  
pp. 1494-1506 ◽  
Author(s):  
Guo-wei Zhong ◽  
Ping Jiang ◽  
Wei-ran Qiao ◽  
Yuan-wei Zhang ◽  
Wen-fan Wei ◽  
...  
Keyword(s):  
Aspergillus Nidulans ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Hyphal Growth ◽  
Negative Regulator ◽  
Regulatory Subunit ◽  
Content Type ◽  
Regulatory Subunits ◽  
Pp2a Activity ◽  
Phosphatase 2A

ABSTRACTProtein phosphatase 2A (PP2A) is a major intracellular protein phosphatase that regulates multiple aspects of cell growth and metabolism. Different activities of PP2A and subcellular localization are determined by its regulatory subunits. Here we identified and characterized the functions of two protein phosphatase regulatory subunit homologs, ParA and PabA, inAspergillus nidulans. Our results demonstrate that ParA localizes to the septum site and that deletion ofparAcauses hyperseptation, while overexpression ofparAabolishes septum formation; this suggests that ParA may function as a negative regulator of septation. In comparison, PabA displays a clear colocalization pattern with 4′,6-diamidino-2-phenylindole (DAPI)-stained nuclei, and deletion ofpabAinduces a remarkable delayed-septation phenotype. BothparAandpabAare required for hyphal growth, conidiation, and self-fertilization, likely to maintain normal levels of PP2A activity. Most interestingly,parAdeletion is capable of suppressing septation defects inpabAmutants, suggesting that ParA counteracts PabA during the septation process. In contrast, double mutants ofparAandpabAled to synthetic defects in colony growth, indicating that ParA functions synthetically with PabA during hyphal growth. Moreover, unlike the case for PP2A-Par1 and PP2A-Pab1 in yeast (which are negative regulators that inactivate the septation initiation network [SIN]), loss of ParA or PabA fails to suppress defects of temperature-sensitive mutants of the SEPH kinase of the SIN. Thus, our findings support the previously unrealized evidence that the B-family subunits of PP2A have comprehensive functions as partners of heterotrimeric enzyme complexes of PP2A, both spatially and temporally, inA. nidulans.

scholarly journals Autoantibody to MDM2: A Potential Serological Marker of Systemic Lupus Erythematosus

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yuan Liu ◽  
Liping Dai ◽  
Weihong Liu ◽  
Guixiu Shi ◽  
Jianying Zhang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immunofluorescence Assay ◽  
Negative Regulator ◽  
Autoimmune Response ◽  
Nuclear Staining ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
High Prevalence ◽  
Healthy Persons

Introduction.Systemic lupus erythematosus (SLE) is one of the systemic autoimmune diseases characterized by the polyclonal autoantibody production. The human homologue of the mouse double minute 2 (MDM2) is well known as the negative regulator of p53. MDM2 has been reported to be overexpressed in SLE animal model and to promote SLE. Since abnormally expressed proteins can induce autoimmune response, anti-MDM2 autoantibody was examined in SLE patients.Methods.Anti-MDM2 antibody in sera from 43 SLE patients and 69 healthy persons was investigated by ELISA. Positive samples were further confirmed by western blotting. The immunological feathers of anti-MDM2 positive sera were analyzed by indirect immunofluorescence assay. Anti-p53 was also investigated in SLE patients by ELISA, and the correlation of anti-MDM2 and anti-p53 was analyzed.Results.The presence of anti-MDM2 in SLE patients was 23.30%, much higher than normal healthy persons (4.30%). These anti-MDM2 positive sera present a nuclear staining pattern. The presence of anti-p53 in SLE patients was 39.50%, and the titer of anti-MDM2 was positively correlated with anti-p53 in SLE patients.Conclusions.Anti-MDM2 autoantibody was detected at high prevalence in SLE patients. The detection of anti-MDM2 in SLE patients should be clinically useful.

scholarly journals A protein phosphatase 2A catalytic subunit is a negative regulator of abscisic acid signalling1

2007 ◽  
Vol 51 (5) ◽  
pp. 763-778 ◽  
Author(s):  
Mónica Pernas ◽  
Gloria García-Casado ◽  
Enrique Rojo ◽  
Roberto Solano ◽  
Jose J. Sánchez-Serrano
Keyword(s):  
Abscisic Acid ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Catalytic Subunit ◽  
Negative Regulator ◽  
Phosphatase 2A
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