Vol. 02, 2015

Evolutionary rewiring of bacterial regulatory networks

Tiffany B. Taylor1,*, Geraldine Mulley1, Liam J. McGuffin1, Louise J. Johnson1, Michael A. Brockhurst2, Tanya Arseneault1,3, Mark W. Silby4 and Robert W. Jackson1,5

Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks – homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. This article discusses Taylor, et al. Science (2015), 347(6225), reporting mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but which come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs.

Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast

Natalie K. Jones1,2,4,#, Nagla T.T. Arab1,3,#, Rawan Eid1,3,#, Nada Gharib1,5, Sara Sheibani1,2,6, Hojatollah Vali2, Chamel Khoury1, Alistair Murray1,2, Eric Boucher2, Craig A. Mandato2, Paul G. Young3 and Michael T. Greenwood1

The human Thyroid Cancer-1 (hTC-1) protein, also known as C8orf4 was initially identified as a gene that was up-regulated in human thyroid cancer. This article reports that hTC-1 is a peptide that prevents the effects of over-expressing Bax in yeast. In sum, the results indicate that hTC-1 is a pro-survival protein that retains its function when heterologously expressed in yeast. Thus yeast is a useful model to characterize the potential roles in cell death and survival of cancer related genes.

Wanted Plasmodium falciparum, dead or alive

Fatimata Sow1, Mary Nyonda1, Anne-Lise Bienvenu1, 2, Stephane Picot1, 2

In this article, mechanisms of cell death in unicellular parasites are discussed, focussing on “programmed cell death” in Plasmodium.

Yeast as a tool to explore cathepsin D function

H. Pereira1, C.S.F. Oliveira1,2, L. Castro1, A. Preto1, S. R. Chaves1,#, M. Côrte-Real1,#

Cathepsin D has garnered increased attention in recent years, mainly since it has been associated with several human pathologies. This review summarizes how cathepsin D can have both anti- and pro-survival functions depending on its proteolytic activity, cellular context and stress stimulus.

Toxoplasma control of host apoptosis: the art of not biting too hard the hand that feeds you

Sébastien Besteiro

Toxoplasma gondii is an obligate intracellular parasite that is able to infect a multitude of different vertebrate hosts and can survive in virtually any nucleated cell. Here, the authors discuss the article "Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly" by Graumann et al. (2015, Microbial Cell).

A safety catch for ornithine decarboxylase degradation

Christof Taxis

Feedback inhibition is a common mechanism to adjust the activity of an enzyme in accordance with the abundance of a product. This article comments on the study "Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome" by Beenukumar et al. (2015), Microbial Cell.

Coordinate responses to alkaline pH stress in budding yeast

Albert Serra-Cardona, David Canadell and Joaquín Ariño

This review summarizes the modulation of a substantial number of signaling pathways whose participate in the alkaline response in yeast. These regulatory inputs involve not only the conserved Rim101/PacC pathway, but also the calcium-activated phosphatase calcineurin, the Wsc1-Pkc1-Slt2 MAP kinase, the Snf1 and PKA kinases and oxidative stress-response pathways.

Handcuffs for bacteria – NDP52 orchestrates xenophagy of intracellular Salmonella

Pauline Verlhac1,2,3,4,5, Christophe Viret1,2,3,4,5 and Mathias Faure1,2,3,4,5

This microreview discusses the article "Autophagy Receptor NDP52 Regulates Pathogen-Containing Autophagosome Maturation" by Verlhac et al. (2015), Cell Host Microbe.

Struggling for breath in Sherbrooke: 1st Symposium on “One mitochondrion, many diseases” in Sherbrooke, Québec, Canada, March 11th, 2015

Ralf J. Braun1,#, Verónica I. Dumit2,3,#, Cécile Monpays4, Xavier Roucou5, Daniel Serrano6, Julie St-Pierre7, Paula J. Waters8, Ian Bates9, and Denis Gris10

This meeting report summarizes discussions during the "1st symposium on “One mitochondrion, many diseases," which took place in Sherbrooke in southern Québec in 2015.

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Targeting of chromatin readers: a novel strategy used by the Shigella flexneri virulence effector OspF to reprogram transcription

Habiba Harouz, Christophe Rachez, Benoit Meijer, Christian Muchardt, Laurence Arbibe.

In this microreview, the authors discuss the article "Shigella flexneri targets the HP1γ subcode through the phosphothreoninelyase OspF" by Harouz et al. (2014), EMBO J, 22 : 2606-2622.

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From the baker to the bedside: yeast models of Parkinson’s disease

Regina Menezes1,2, Sandra Tenreiro3,5, Diana Macedo2, Cláudia N. Santos1,2, Tiago Fleming Outeiro4,5,6

The baker’s yeast Saccharomyces cerevisiae has been extensively explored for our understanding of fundamental cell biology processes highly conserved in the eukaryotic kingdom. This review provides a brief historical perspective on the emergence of yeast as an experimental model and on how the field evolved to exploit the potential of the model for tackling the intricacies of various human diseases. In particular, the authors focus on existing yeast models of the molecular underpinnings of Parkinson’s disease (PD), focusing primarily on the central role of protein quality control systems.

Why are essential genes essential? – The essentiality of Saccharomyces genes

Zhaojie Zhang and Qun Ren

Essential genes are defined as required for the survival of an organism or a cell. This article reviews and analyzes the levels of essentiality of the Saccharomyces cerevisiae genes and groups the genes into four categories: (1) Conditional essential: essential only under certain circumstances or growth conditions; (2) Essential: required for survival under optimal growth conditions; (3) Redundant essential: synthetic lethal due to redundant pathways or gene duplication; and (4) Absolute essential: the minimal genes required for maintaining a cellular life under a stress-free environment. The essential and non-essential functions of the essential genes are further analyzed.

Evolutionary rewiring of bacterial regulatory networks

Tiffany B. Taylor1,*, Geraldine Mulley1, Liam J. McGuffin1, Louise J. Johnson1, Michael A. Brockhurst2, Tanya Arseneault1,3, Mark W. Silby4 and Robert W. Jackson1,5

Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks – homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. This article discusses Taylor, et al. Science (2015), 347(6225), reporting mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but which come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs.

Wanted Plasmodium falciparum, dead or alive

Fatimata Sow1, Mary Nyonda1, Anne-Lise Bienvenu1, 2, Stephane Picot1, 2

In this article, mechanisms of cell death in unicellular parasites are discussed, focussing on “programmed cell death” in Plasmodium.

Yeast as a tool to explore cathepsin D function

H. Pereira1, C.S.F. Oliveira1,2, L. Castro1, A. Preto1, S. R. Chaves1,#, M. Côrte-Real1,#

Cathepsin D has garnered increased attention in recent years, mainly since it has been associated with several human pathologies. This review summarizes how cathepsin D can have both anti- and pro-survival functions depending on its proteolytic activity, cellular context and stress stimulus.

Coordinate responses to alkaline pH stress in budding yeast

Albert Serra-Cardona, David Canadell and Joaquín Ariño

This review summarizes the modulation of a substantial number of signaling pathways whose participate in the alkaline response in yeast. These regulatory inputs involve not only the conserved Rim101/PacC pathway, but also the calcium-activated phosphatase calcineurin, the Wsc1-Pkc1-Slt2 MAP kinase, the Snf1 and PKA kinases and oxidative stress-response pathways.

Handcuffs for bacteria – NDP52 orchestrates xenophagy of intracellular Salmonella

Pauline Verlhac1,2,3,4,5, Christophe Viret1,2,3,4,5 and Mathias Faure1,2,3,4,5

This microreview discusses the article "Autophagy Receptor NDP52 Regulates Pathogen-Containing Autophagosome Maturation" by Verlhac et al. (2015), Cell Host Microbe.

Struggling for breath in Sherbrooke: 1st Symposium on “One mitochondrion, many diseases” in Sherbrooke, Québec, Canada, March 11th, 2015

Ralf J. Braun1,#, Verónica I. Dumit2,3,#, Cécile Monpays4, Xavier Roucou5, Daniel Serrano6, Julie St-Pierre7, Paula J. Waters8, Ian Bates9, and Denis Gris10

This meeting report summarizes discussions during the "1st symposium on “One mitochondrion, many diseases," which took place in Sherbrooke in southern Québec in 2015.

Understanding grapevine-microbiome interactions: implications for viticulture industry

Iratxe Zarraonaindia1,2 and Jack A. Gilbert3,4,5,6

This microreview discusses the article "The soil microbiome influences grapevine-associated microbiota" by Zarraonaindia et al. (2015), MBio, which reports that the grapevine-associated microbiota depends on the soil microbiome.

Groupthink: chromosomal clustering during transcriptional memory

Kevin A. Morano

In this article, the authors comment on the study "NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering." by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.

Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration

Amit Shrestha1, 2 and Lynn A. Megeney1, 2, 3

Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.

Starting with a degron: N-terminal formyl-methionine of nascent bacterial proteins contributes to their proteolytic control

R. Jürgen Dohmen

In this article, the author comments on the study "Formyl-methionine as a degradation signal at the N-termini of bacterial proteins." by Piatkov et al. (Microbial Cell, 2015), discussing a novel N-terminal degradation signal (N-degron) that targets nascent proteins for degradation in Escherichia coli by a new branch of the bacterial N-end rule pathway, termed the fMet/N-end rule pathway

Elongation factor-P at the crossroads of the host-endosymbiont interface

Andrei Rajkovic1, Anne Witzky2, William Navarre3, Andrew J. Darwin4 and Michael Ibba5

Elongation factor P (EF-P) is an ancient bacterial translational factor that aids the ribosome in polymerizing oligo-prolines. EF-P structurally resembles tRNA and binds in-between the exit and peptidyl sites of the ribosome to accelerate the intrinsically slow reaction of peptidyl-prolyl bond formation. Recent studies have identified in separate organisms, two evolutionarily convergent EF-P post-translational modification systems (EPMS), split predominantly between gammaproteobacteria, and betaproteobacteria. Here, the authors highlight the recent discoveries made regarding EPMSs, with a focus on how these incomplete modification pathways shape or have been shaped by the endosymbiont-host relationship.

Feelin’ it: Differential oxidative stress sensing mediated by Cyclin C

W. Scott Moye-Rowley

Microbial cells that live exposed directly to their environmental milieu are faced with the challenge of adapting to the dynamic stress conditions that will inevitably be encountered. These stress conditions may vary over wide ranges and the most efficient responses would be tuned to produce a proportional buffering change. A mild stress would most efficiently be dealt with by a mild metabolic reprogramming that would prevent serious damage. A more severe environmental challenge would demand a more dramatic cellular compensatory response.

Subverting lysosomal function in Trypanosoma brucei

Sam Alsford

This article discusses Koh et al. (2015) "The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei (Microbial Cell 2(8): 288-298).

Toxoplasma control of host apoptosis: the art of not biting too hard the hand that feeds you

Sébastien Besteiro

Toxoplasma gondii is an obligate intracellular parasite that is able to infect a multitude of different vertebrate hosts and can survive in virtually any nucleated cell. Here, the authors discuss the article "Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly" by Graumann et al. (2015, Microbial Cell).

A safety catch for ornithine decarboxylase degradation

Christof Taxis

Feedback inhibition is a common mechanism to adjust the activity of an enzyme in accordance with the abundance of a product. This article comments on the study "Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome" by Beenukumar et al. (2015), Microbial Cell.

Fancy a gene? A surprisingly complex evolutionary history of peroxiredoxins.

Alena Zíková1,2, Miroslav Oborník1,2,3 and Julius Lukeš1,2,4

In this comment, the authors discuss the article "Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites" (Djuika et al., Microbial Cell 2015).

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Targeting of chromatin readers: a novel strategy used by the Shigella flexneri virulence effector OspF to reprogram transcription

December 28, 2014

In this microreview, the authors discuss the article "Shigella flexneri targets the HP1γ subcode through the phosphothreoninelyase OspF" by Harouz et al. (2014), EMBO J, 22 : 2606-2622.

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