Research, Research Reports
In Entamoeba histolytica, a BspA family protein is required for chemotaxis toward tumour necrosis factor
Anne Silvestre1, 2, 3, 4, Aurélie Plaze1, 2, Patricia Berthon3, 4, Roman Thibeaux1, 2, Nancy Guillen1, 2 and Elisabeth Labruyère1, 2
Background: Entamoeba histolytica cell migration is essential for the development of human amoebiasis (an infectious disease characterized by tissue invasion and destruction). The tissue inflammation associated with tumour necrosis factor (TNF) secretion by host cells is a well-documented feature of amoebiasis. Tumour necrosis factor is a chemoattractant for E. histolytica, and the parasite may have a TNF receptor at its cell surface. Methods: confocal microscopy, RNA Sequencing, bioinformatics, RNA antisense techniques and histological analysis of human colon explants were used to characterize the interplay between TNF and E. histolytica. Results: an antibody against human TNF receptor 1 (TNFR1) stained the E. histolytica trophozoite...
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.
Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome
R. Roshini Beenukumar1,#, Daniela Gödderz1,2,#, R. Palanimurugan1,3, and R. Jürgen Dohmen1
Ornithine decarboxylase (ODC), a ubiquitin-independent substrate of the proteasome, is a homodimeric protein with a rate-limiting function in polyamine biosynthesis. Polyamines regulate ODC levels by a feedback mechanism mediated by ODC antizyme (OAZ). Higher cellular polyamine levels trigger the synthesis of OAZ and also inhibit its ubiquitin-dependent proteasomal degradation. OAZ binds ODC monomers and targets them to the proteasome. Here, we report that polyamines, aside from their role in the control of OAZ synthesis and stability, directly enhance OAZ-mediated ODC degradation by the proteasome. Using a stable mutant of OAZ, we show that polyamines promote ODC degradation in Saccharomyces cerevisiae cells even when OAZ levels are not changed. Furthermore, polyamines stimulated the in vitro degradation of ODC by the...
Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly
Kristin Graumann1,3,#, Frieder Schaumburg1,4,#, Thomas F. Reubold2, Diana Hippe1, Susanne Eschenburg2 and Carsten G. K. Lüder1
Inhibition of programmed cell death pathways of mammalian cells often facilitates the sustained survival of intracellular microorganisms. The apicomplexan parasite Toxoplasma gondii is a master regulator of host cell apoptotic pathways. Here, we have characterized a novel anti-apoptotic activity of T. gondii. Using a cell-free cytosolic extract model, we show that T. gondii interferes with the activities of caspase 9 and caspase 3/7 which have been induced by exogenous cytochrome c and dATP. Proteolytic cleavage of caspases 9 and 3 is also diminished suggesting inhibition of holo-apoptosome function. Parasite infection of Jurkat T cells and subsequent triggering of apoptosome formation by exogenous cytochrome c in vitro and in vivo indicated that...
Exogenous folates stimulate growth and budding of Candida glabrata
Afsaneh Porzoor and Ian G. Macreadie
Folate, vitamin B9, is well recognized as being essential for cell growth. The utilization of folate is common to all cells, but the source of it may be quite different. This article reports a novel response of yeast to folates that may increase the utility of yeast as a model to study folate transport and signaling.
Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism
Camilla Ceccatelli Berti1, Cristina Dallabona1, Mirca Lazzaretti1, Sabrina Dusi2, Elena Tosi1, Valeria Tiranti2, Paola Goffrini1
Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA), namely PKAN and CoPAN. Yeast expressing a pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.
Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites
Carine F. Djuika1, Jaime Huerta-Cepas2, Jude M. Przyborski3, Sophia Deil1, Cecilia P. Sanchez1, Tobias Doerks2, Peer Bork2, Michael Lanzer1 and Marcel Deponte1
Horizontal gene transfer has emerged as a crucial driving force for the evolution of eukaryotes. This also includes Plasmodium falciparum and related economically and clinically relevant apicomplexan parasites, whose rather small genomes have been shaped not only by natural selection in different host populations but also by horizontal gene transfer following endosymbiosis. However, there is rather little reliable data on horizontal gene transfer between animal hosts or bacteria and apicomplexan parasites. Here we show that apicomplexan homologues of peroxiredoxin 5 (Prx5) have a prokaryotic ancestry and therefore represent a special subclass of Prx5 isoforms in eukaryotes. Using two different immunobiochemical approaches, we found that...
Two distinct and competitive pathways confer the cellcidal actions of artemisinins
Chen Sun#, Jian Li#, Yu Cao, Gongbo Long and Bing Zhou
The biological actions of artemisinin (ART), an antimalarial drug derived from Artemisia annua, remain poorly understood and controversial. This article concludes that ARTs are endowed with two major and distinct types of properties: a potent and specific mitochondria-dependent reaction and a more general and less specific heme-mediated reaction. The competitive nature of these two actions could be explained by their shared source of the consumable ARTs, so that inhibition of the heme-mediated degradation pathway would enable more ARTs to be available for the mitochondrial action. These properties of ARTs can be used to interpret the divergent antimalarial and anticancer actions of ARTs.
A time-resolved high-throughput screening of fission yeast deletion mutants for oxidative stress resistance
July 22, 2026
By capturing dynamic trajectories rather than static outcomes, this study exposes hidden layers of growth under oxidative stress and identifies new genetic determinants of cellular resilience in fission yeast.
Microwave-assisted preparation of yeast cells for ultrastructural analysis by electron microscopy
November 18, 2024
Budding yeast Saccharomyces cerevisiae is widely used as a model organism to study the biogenesis and architecture of organellar membranes, which can be visualized by transmission electron microscopy (TEM).
Direct detection of stringent alarmones (pp)pGpp using malachite green
August 5, 2024
In this study, we demonstrate the surprising discovery of a commercially available, low-cost malachite green (MG) detection kit, originally designed for orthophosphate (Pi) detection, for detecting (p)ppGpp and its analogues, especially pGpp
Unresolved mystery of cyclic nucleotide second messengers, periplasmic acid phosphatases and bacterial natural competence
July 18, 2024
In this study we aimed to identify the promotors responsible for the expression of the non-specific acid phosphatase AphA during different starvation conditions, to confirm the requirement of the cAMP-dependent CRP regulon for aphA expression, and to finally identify regulators of its expression.
Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2
August 8, 2023
We show here that apart from its effector role for Elongator-dependent tRNA modification in yeast, Kti13 alias Dph8 also operates in step one of the diphthamide modification pathway.
Atg1, a key regulator of autophagy, functions to promote MAPK activation and cell death upon calcium overload in fission yeast
May 10, 2023
Here, we provide evidence that the fission yeast Atg1 regulates cell death responses upon intracellular calcium load in addition to its role in promoting Pmk1 MAPK.
Investigating the role of G-quadruplexes at Saccharomyces cerevisiae telomeres
May 19, 2022
In this study, the authors examine the in vivo relevance of telomeric G-quadruplexes in the budding yeast Saccharomyces cerevisiae by expressing a mutant telomerase RNA subunit (tlc1-tm) that introduces mutant telomeric repeats instead to the distal ends of telomeres. (...)