MEGA-CC: computing core of molecular evolutionary genetics analysis program for automated and iterative data analysis

Kumar, Sudhir; Stecher, Glen; Peterson, Daniel S.; Tamura, Koichiro

doi:10.1093/bioinformatics/bts507

Cited by 316 publications

(242 citation statements)

References 3 publications

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“…Sequences with the greatest homology to the PF3D7_1305500 ORF were retrieved and used to build the multiple alignments using ClustalW (40,41). The evolutionary history was inferred using a phylogenetic tree created using the neighbor-joining method with 1,000 bootstrap replicates MEGA5 (42)(43)(44).…”

Section: Methodsmentioning

confidence: 99%

Atypical Mitogen-Activated Protein Kinase Phosphatase Implicated in Regulating Transition from Pre-S-Phase Asexual Intraerythrocytic Development of Plasmodium falciparum

et al. 2013

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Intraerythrocytic development of the human malaria parasite Plasmodium falciparum appears as a continuous flow through growth and proliferation. To develop a greater understanding of the critical regulatory events, we utilized piggyBac insertional mutagenesis to randomly disrupt genes. Screening a collection of piggyBac mutants for slow growth, we isolated the attenuated parasite C9, which carried a single insertion disrupting the open reading frame (ORF) of PF3D7_1305500. This gene encodes a protein structurally similar to a mitogen-activated protein kinase (MAPK) phosphatase, except for two notable characteristics that alter the signature motif of the dual-specificity phosphatase domain, suggesting that it may be a low-activity phosphatase or pseudophosphatase. C9 parasites demonstrated a significantly lower growth rate with delayed entry into the S/M phase of the cell cycle, which follows the stage of maximum PF3D7_1305500 expression in intact parasites. Genetic complementation with the full-length PF3D7_1305500 rescued the wild-type phenotype of C9, validating the importance of the putative protein phosphatase PF3D7_1305500 as a regulator of pre-S-phase cell cycle progression in P. falciparum. Malaria caused by Plasmodium falciparum infection is the major type of severe malaria and results in hundreds of thousands of deaths each year and hundreds of millions of clinical illnesses (1, 2). Within the blood of infected individuals, asexual forms of the intraerythrocytic parasite grow rapidly through successive cycles of growth and proliferation. In each asexual generation, active entry into erythrocytes is followed by a growth phase culminating in dynamic release of erythrocyte-invading merozoites. The Plasmodium mitotic cycle is not fully understood and differs from the well-defined models established in yeast and mammalian cells (3). Observing the exact mitotic transitions during the cycle has been difficult due to variations in processes such as chromatid segregation, nuclear division, and spindle formation (4). However, this pattern of development has been observed in other members of the Apicomplexa, such as Toxoplasma gondii and Eimeria tenella, demonstrating the importance and conservation of this process across the phylum (5, 6).In eukaryotic systems, phosphorylation cascades are critical to cellular development and depend on the coordinated activity of kinases, which are in turn modulated by the activity of phosphatases. There is growing evidence that kinases are critical regulators of cell growth and development in Plasmodium species (7-9). Plasmodium kinases, for example, have been found to be involved with the initial invasion of host cells in addition to egress and differentiation (6, 10). Additional studies have identified kinases in phosphorylation cascades of the gametocyte-ookinete-oocyst transition in the mosquito midgut (11)(12)(13)(14)(15)(16)(17). In contrast, few studies have described the phosphatases involved in these processes, which would understandably function with kinases to coregul...

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Section: Methodsmentioning

confidence: 99%

Atypical Mitogen-Activated Protein Kinase Phosphatase Implicated in Regulating Transition from Pre-S-Phase Asexual Intraerythrocytic Development of Plasmodium falciparum

et al. 2013

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“…For visualization and editing of the alignment, Jalview was used (Waterhouse et al, 2009). LG+G was selected as the best fitting amino acid substitution model according to the Bayesian Information Criterion in MEGA-CC Model Selection analysis (Kumar et al, 2012). To reconstruct the phylogeny, the maximum likelihood (ML) algorithm with a bootstrap test (1000 replications) implemented in MEGA-CC was used (additional settings: no.…”

Section: Phylogenetic Analysismentioning

confidence: 99%

Changes in PUB22 Ubiquitination Modes Triggered by MITOGEN-ACTIVATED PROTEIN KINASE3 Dampen the Immune Response

et al. 2017

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Crosstalk between posttranslational modifications, such as ubiquitination and phosphorylation, play key roles in controlling the duration and intensity of signaling events to ensure cellular homeostasis. However, the molecular mechanisms underlying the regulation of negative feedback loops remain poorly understood. Here, we uncover a pathway in Arabidopsis thaliana by which a negative feedback loop involving the E3 ubiquitin ligase PUB22 that dampens the immune response is triggered by MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3), best known for its function in the activation of signaling. PUB22's stability is controlled by MPK3-mediated phosphorylation of residues localized in and adjacent to the E2 docking domain. We show that phosphorylation is critical for stabilization by inhibiting PUB22 oligomerization and, thus, autoubiquitination. The activity switch allows PUB22 to dampen the immune response. This regulatory mechanism also suggests that autoubiquitination, which is inherent to most single unit E3s in vitro, can function as a self-regulatory mechanism in vivo.

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“…. Multiple sequence alignments were created with the Molecular Evolutionary Genetics Analysis (MEGA) software version 5.1 (Kumar et al, 2012). Sequence presentation and shading of multiple sequence alignments was performed using the LaTEX TEXshade package (Beitz, 2000).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Global metabolite analysis of the land snail Theba pisana hemolymph during active and aestivated states

Bose

Centurion

Hodson

et al. 2016

Comparative Biochemistry and Physiology Part D: Genomics and Pr

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MEGA-CC: computing core of molecular evolutionary genetics analysis program for automated and iterative data analysis

Abstract: http://www.megasoftware.net/.

Cited by 316 publications

References 3 publications

Atypical Mitogen-Activated Protein Kinase Phosphatase Implicated in Regulating Transition from Pre-S-Phase Asexual Intraerythrocytic Development of Plasmodium falciparum

Atypical Mitogen-Activated Protein Kinase Phosphatase Implicated in Regulating Transition from Pre-S-Phase Asexual Intraerythrocytic Development of Plasmodium falciparum

Changes in PUB22 Ubiquitination Modes Triggered by MITOGEN-ACTIVATED PROTEIN KINASE3 Dampen the Immune Response

Global metabolite analysis of the land snail Theba pisana hemolymph during active and aestivated states

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