Who's in charge here? Regulating cell cycle regulators

Bowers, Lisa M.; Shapland, Elaine B.; Ryan, Kathleen R.

doi:10.1016/j.mib.2008.09.019

Cited by 17 publications

(17 citation statements)

References 49 publications

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“…2A and B). Because the length of the cell cycle varies among growing cells (even within the same agarose-padded slide), it remained unclear if delocalization preceded or followed cytokinesis (i.e., the cytoplasmic compartmentalization of the predivisional cell), a key cell cycle event that determines the fate of daughter cells (2,5,7,16,20,42). Cytokinesis triggers many changes in the cell, including the release of DivK from the new pole into the swarmer cell compartment, while DivK remains localized at the old pole in the stalked cell compartment (27,37).…”

Section: Resultsmentioning

confidence: 99%

“…The alphaproteobacterium Caulobacter crescentus provides a model system that has been particularly useful for unraveling the bacterial cell cycle (2,5,7,16,20,42). Its life cycle is characterized by an asymmetric cell division that yields two distinct daughter cells, the motile swarmer cell and the sessile stalked cell.…”

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confidence: 99%

“…His-Asp phosphorelay systems, which are one of the predominant stimulus response systems in prokaryotic cells (50), play an essential role in coordinating cell cycle progression in C. crescentus (2,5,42). The membrane-bound hybrid histidine kinase CckA is involved in two interconnected phosphorelays that regulate the DNA-binding activity of the CtrA response regulator (Fig.…”

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confidence: 99%

“…The response regulator CtrA is a key factor in driving the C. crescentus cell cycle, and as such its activity is tightly regulated at the transcriptional level and at the posttranslational level (2,5), leading to the periodicity of active CtrAϳP during the cell cycle (Fig. 1A).…”

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Polar Localization of the CckA Histidine Kinase and Cell Cycle Periodicity of the Essential Master Regulator CtrA in Caulobacter crescentus

2010

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The phosphorylated form of the response regulator CtrA represses DNA replication initiation and regulates the transcription of about 100 cell cycle-regulated genes in Caulobacter crescentus. CtrA activity fluctuates during the cell cycle, and its periodicity is a key element of the engine that drives cell cycle progression. The histidine kinase CckA controls the phosphorylation not only of CtrA but also of CpdR, whose unphosphorylated form promotes CtrA proteolysis. Thus, CckA has a central role in establishing the cell cycle periodicity of CtrA activity by controlling both its phosphorylation and stability. Evidence suggests that the polar localization of CckA during the cell cycle plays a role in CckA function. However, the exact pattern of CckA localization remains controversial. Here, we describe a thorough, quantitative analysis of the spatiotemporal distribution of a functional and chromosomally produced CckA-monomeric green fluorescent protein fusion that affects current models of cell cycle regulation. We also identify two cis-acting regions in CckA that are important for its proper localization and function. The disruption of a PAS-like motif in the sensor domain affects the stability of CckA accumulation at the poles. This is accompanied by a partial loss in CckA function. Shortening an extended linker between ␤-sheets within the CckA catalysis-assisting ATP-binding domain has a more severe effect on CckA polar localization and function. This mutant strain exhibits a dramatic cell-to-cell variability in CpdR levels and CtrA cell cycle periodicity, suggesting that the cell cycle-coordinated polar localization of CckA may be important for the robustness of signal transduction and cell cycle progression.

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Polar Localization of the CckA Histidine Kinase and Cell Cycle Periodicity of the Essential Master Regulator CtrA in Caulobacter crescentus

2010

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“…In C. crescentus, the activity of CtrA is controlled through transcriptional, phosphorylation, and proteolytic regulation (8). There is a complex system controlling the activation and turnover of CtrA, involving the histidine kinase proteins DivJ, DivL, PleC, and CckA, the histidine phosphotransferase ChpT, the response regulators DivK and CpdR, the protease ClpXP, and a protein of unknown function, RcdA.…”

Section: Discussionmentioning

confidence: 99%

Loss of the Response Regulator CtrA Causes Pleiotropic Effects on Gene Expression but Does Not Affect Growth Phase Regulation in Rhodobacter capsulatus

Mercer

Callister²,

Lipton³

et al. 2010

J Bacteriol

102

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The purple nonsulfur photosynthetic bacterium Rhodobacter capsulatus has been extensively studied for its metabolic versatility as well as for production of a gene transfer agent called RcGTA. Production of RcGTA is highest in the stationary phase of growth and requires the response regulator protein CtrA. The CtrA protein in Caulobacter crescentus has been thoroughly studied for its role as an essential, master regulator of the cell cycle. Although the CtrA protein in R. capsulatus shares a high degree of sequence similarity with the C. crescentus protein, it is nonessential and clearly plays a different role in this bacterium. We have used transcriptomic and proteomic analyses of wild-type and ctrA mutant cultures to identify the genes dysregulated by the loss of CtrA in R. capsulatus. We have also characterized gene expression differences between the logarithmic and stationary phases of growth. Loss of CtrA has pleiotropic effects, with dysregulation of expression of ϳ6% of genes in the R. capsulatus genome. This includes all flagellar motility genes and a number of other putative regulatory proteins but does not appear to include any genes involved in the cell cycle. Quantitative proteomic data supported 88% of the CtrA transcriptome results. Phylogenetic analysis of CtrA sequences supports the hypothesis of an ancestral ctrA gene within the alphaproteobacteria, with subsequent diversification of function in the major alphaproteobacterial lineages.The purple nonsulfur bacterium Rhodobacter capsulatus is a model organism for various aspects of bacterial physiology, such as bioenergetics and N 2 fixation, and also engages in an unusual mechanism of genetic exchange, carried out by a bacteriophage-like element called the R. capsulatus gene transfer agent (RcGTA) (34, 56). The production of RcGTA is maximal in the stationary phase of growth of R. capsulatus cultures (49) and is regulated by at least 2 distinct signaling systems, one through quorum sensing of a long chain acyl-homoserine lactone (43) and the other involving the response regulator protein CtrA (30).The CtrA protein was first characterized for Caulobacter crescentus (41), where it is essential for viability and acts as a master regulator of the cell cycle (reviewed in reference 45), controlling at least 25% (144 of 553) of the genes involved in cell cycle progression (31). Despite sharing remarkable sequence identity (71%) with the CtrA protein from C. crescentus, the R. capsulatus protein has a very different role because it is not essential and does not appear to be involved in cell cycle processes. One function of CtrA in common to the two species is the regulation of expression of genes that encode the flagellum (29, 41). The ctrA genes of Sinorhizobium meliloti (3), Brucella abortus (6), and Ruegeria sp. strain TM1040 (36) have also been studied. Similarly to C. crescentus and R. capsulatus CtrA, Ruegeria CtrA controls motility (36). A search of the GenBank database reveals that convincing homologs which share Ͼ50% identity with the C. crescen...

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Impact of EMS outreach: Successful developments in Latin America

Olivero

Larramendy

Soloneski

et al. 2010

Environ and Mol Mutagen

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This collection of articles was inspired by the long-standing relationship between the Environmental Mutagen Society and Latin American scientists, and by the program for the 39th Environmental Mutagen Society meeting in Puerto Rico in 2008, which included a symposium featuring “South of the border” scientists. This collection, compiled by Graciela Spivak and Ofelia Olivero, both originally from Argentina, highlights scientists who work in or were trained in Latin American countries and in Puerto Rico in a variety of scientific specialties related to DNA repair and cancer susceptibility, genomic organization and stability, genetic diversity, and environmental contaminants.

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Who's in charge here? Regulating cell cycle regulators

Cited by 17 publications

References 49 publications

Polar Localization of the CckA Histidine Kinase and Cell Cycle Periodicity of the Essential Master Regulator CtrA in Caulobacter crescentus

Polar Localization of the CckA Histidine Kinase and Cell Cycle Periodicity of the Essential Master Regulator CtrA in Caulobacter crescentus

Loss of the Response Regulator CtrA Causes Pleiotropic Effects on Gene Expression but Does Not Affect Growth Phase Regulation in Rhodobacter capsulatus

Impact of EMS outreach: Successful developments in Latin America

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