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T A Trendeleva, R A Zvyagilskaya
Mitochondria perform many essential functions in eukaryotic cells. Being the main producers of ATP and the site of many catabolic and anabolic reactions, they participate in intracellular signaling, proliferation, aging, and formation of reactive oxygen species. Mitochondrial dysfunction is the cause of many diseases and even cell death. The functioning of mitochondria in vivo is impossible without interaction with other cellular compartments. Mitochondrial retrograde signaling is a signaling pathway connecting mitochondria and the nucleus...
February 2018: Biochemistry. Biokhimii︠a︡
Jeremy Whelan, Allan Hackshaw, Anne McTiernan, Robert Grimer, David Spooner, Jessica Bate, Andreas Ranft, Michael Paulussen, Herbert Juergens, Alan Craft, Ian Lewis
Background: Two national clinical trial groups, United Kingdom Children's Cancer and Leukaemia Group (CCLG) and the German Paediatric Oncology and Haematology Group (GPOH) together undertook a randomised trial, EICESS-92, which addressed chemotherapy options for Ewing's sarcoma. We sought the causes of unexpected survival differences between the study groups. Methods: 647 patients were randomised. Cox regression analyses were used to compare event-free survival (EFS) and overall survival (OS) between the two study groups...
2018: Clinical Sarcoma Research
Zhongfeng Sun, Jiabin Song, Xi'an Xin, Xianan Xie, Bin Zhao
Arbuscular mycorrhizal (AM) fungi are soil-borne fungi belonging to the ancient phylum Glomeromycota and are important symbionts of the arbuscular mycorrhiza, enhancing plant nutrient acquisition and resistance to various abiotic stresses. In contrast to their significant physiological implications, the molecular basis involved is poorly understood, largely due to their obligate biotrophism and complicated genetics. Here, we identify and characterize three genes termed Fm201 , Ri14-3-3 and RiBMH2 that encode 14-3-3-like proteins in the AM fungi Funneliformis mosseae and Rhizophagus irregularis , respectively...
2018: Frontiers in Microbiology
Ravinder Kumar
14-3-3 is a family of relatively low molecular weight, acidic, dimeric proteins, conserved from yeast to metazoans including humans. Apart from their role in diverse cellular processes, these proteins are also known for their role in several clinical implications. Present proteomic and biochemical comparison showed increased abundance and differential phosphorylation of these proteins in meiotic cells. Double deletion of bmh1-/-bmh2-/- leads to complete absence of sporulation with cells arrested at G1/S phase while further incubation of cells in sporulating media leads to cell death...
February 1, 2018: Scientific Reports
Janneke H M Teunissen, Marjolein E Crooijmans, Pepijn P P Teunisse, G Paul H van Heusden
BACKGROUND: Ion homeostasis is an essential property of living organisms. The yeast Saccharomyces cerevisiae is an ideal model organism to investigate ion homeostasis at all levels. In this yeast genes involved in high-affinity phosphate uptake (PHO genes) are strongly induced during both phosphate and potassium starvation, indicating a link between phosphate and potassium homeostasis. However, the signal transduction processes involved are not completely understood. As 14-3-3 proteins are key regulators of signal transduction processes, we investigated the effect of deletion of the 14-3-3 genes BMH1 or BMH2 on gene expression during potassium starvation and focused especially on the expression of genes involved in phosphate uptake...
September 6, 2017: BMC Genomics
Jennifer J Tate, David Buford, Rajendra Rai, Terrance G Cooper
Nitrogen catabolite repression (NCR), the ability of Saccharomyces cerevisiae to use good nitrogen sources in preference to poor ones, derives from nitrogen-responsive regulation of the GATA family transcription activators Gln3 and Gat1 In nitrogen-replete conditions, the GATA factors are cytoplasmic and NCR-sensitive transcription minimal. When only poor nitrogen sources are available, Gln3 is nuclear, dramatically increasing GATA factor-mediated transcription. This regulation was originally attributed to mechanistic Tor protein kinase complex 1 (mTorC1)-mediated control of Gln3 However, we recently showed that two regulatory systems act cumulatively to maintain cytoplasmic Gln3 sequestration, only one of which is mTorC1...
February 2017: Genetics
Andrea Eisenreichova, Martin Klima, Evzen Boura
14-3-3 proteins bind phosphorylated binding partners to regulate several of their properties, including enzymatic activity, stability and subcellular localization. Here, two crystal structures are presented: the crystal structures of the 14-3-3 protein (also known as Bmh1) from the yeast Lachancea thermotolerans in the unliganded form and bound to a phosphopeptide derived from human PI4KB (phosphatidylinositol 4-kinase B). The structures demonstrate the high evolutionary conservation of ligand recognition by 14-3-3 proteins...
November 1, 2016: Acta Crystallographica. Section F, Structural Biology Communications
Yuliya Gryaznova, Ayse Koca Caydasi, Gabriele Malengo, Victor Sourjik, Gislene Pereira
The spindle position checkpoint (SPOC) is a spindle pole body (SPB, equivalent of mammalian centrosome) associated surveillance mechanism that halts mitotic exit upon spindle mis-orientation. Here, we monitored the interaction between SPB proteins and the SPOC component Bfa1 by FRET microscopy. We show that Bfa1 binds to the scaffold-protein Nud1 and the γ-tubulin receptor Spc72. Spindle misalignment specifically disrupts Bfa1-Spc72 interaction by a mechanism that requires the 14-3-3-family protein Bmh1 and the MARK/PAR-kinase Kin4...
May 9, 2016: ELife
Si-Min Yuan, Wen-Chao Nie, Fei He, Zhi-Wen Jia, Xiang-Dong Gao
MARK/PAR-1 protein kinases play important roles in cell polarization in animals. Kin1 and Kin2 are a pair of MARK/PAR-1 orthologs in the budding yeast Saccharomyces cerevisiae. They participate in the regulation of secretion and ER stress response. However, neither the subcellular localization of these two kinases nor whether they may have other cellular functions is clear. Here, we show that Kin2 localizes to the sites of polarized growth in addition to localization on the plasma membrane. The localization to polarity sites is mediated by two targeting domains-TD1 and TD2...
2016: PloS One
Volker Hübscher, Kaivalya Mudholkar, Marco Chiabudini, Edith Fitzke, Tina Wölfle, Dietmar Pfeifer, Friedel Drepper, Bettina Warscheid, Sabine Rospert
Chaperones of the Hsp70 family interact with a multitude of newly synthesized polypeptides and prevent their aggregation. Saccharomyces cerevisiae cells lacking the Hsp70 homolog Ssb suffer from pleiotropic defects, among others a defect in glucose-repression. The highly conserved heterotrimeric kinase SNF1/AMPK (AMP-activated protein kinase) is required for the release from glucose-repression in yeast and is a key regulator of energy balance also in mammalian cells. When glucose is available the phosphatase Glc7 keeps SNF1 in its inactive, dephosphorylated state...
July 8, 2016: Nucleic Acids Research
Michael Bokros, Curtis Gravenmier, Fengzhi Jin, Daniel Richmond, Yanchang Wang
The spindle assembly checkpoint (SAC) monitors chromosome attachment defects, and the assembly of SAC proteins at kinetochores is essential for its activation, but the SAC disassembly process remains unknown. We found that deletion of a 14-3-3 protein, Bmh1, or hyperactivation of Cdc14 early anaphase release (FEAR) allows premature SAC silencing in budding yeast, which depends on a kinetochore protein Fin1 that forms a complex with protein phosphatase PP1. Previous works suggest that FEAR-dependent Fin1 dephosphorylation promotes Bmh1-Fin1 dissociation, which enables kinetochore recruitment of Fin1-PP1...
February 9, 2016: Cell Reports
Pabitra K Parua, Kenneth M Dombek, Elton T Young
In eukaryotes combinatorial activation of transcription is an important component of gene regulation. In the budding yeast Saccharomyces cerevisiae, Adr1-Cat8 and Adr1-Oaf1/Pip2 are pairs of activators that act together to regulate two diverse sets of genes. Transcription activation of both sets is regulated positively by the yeast AMP-activated protein kinase homolog, Snf1, in response to low glucose or the presence of a non-fermentable carbon source and negatively by two redundant 14-3-3 isoforms, Bmh1 and Bmh2...
December 19, 2014: Journal of Biological Chemistry
Joao A Paulo, Steven P Gygi
We applied a multiplexed, MS-based strategy to interrogate the proteome and phosphoproteome of three yeast strains under two growth conditions in triplicate. The yeast proteins brain modulosignalin homologue (Bmh)1 and Bmh2, analogs to the 14-3-3 protein family, have a wide array of cellular functions including the regulation of phosphorylation events. Moreover, rapamycin is a drug that can regulate phosphorylation events. By performing a series of tandem mass tag 10-plex experiments, we investigated the alterations in the proteome and phosphoproteome of wildtype and two deletion strains (bmh1Δ and bmh2Δ) of Saccharomyces cerevisiae treated with rapamycin and DMSO as a control...
January 2015: Proteomics
Qian Liu, Jin-Gen Li, Sheng-Hua Ying, Juan-Juan Wang, Wen-Liang Sun, Chao-Guang Tian, Ming-Guang Feng
Two conserved 14-3-3 proteins orthologous to Saccharomyces cerevisiae Bmh1/2 are poorly understood in filamentous fungi. Here we show that Bmh1 and Bmh2 contribute equally to the fundamental biology and physiology of Beauveria bassiana by targeting many sets of proteins/enzymes. Single Bmh deletion caused similar upregulation of another. Excellent knockdown (∼91%) expressions of Bmh1 in ΔBmh2 and Bmh2 in ΔBmh1 resulted in equally more severe multiphenotypic defects than the single deletions, including G2 /M transition, blastospore size, carbon/nitrogen utilization, conidiation, germination and conidial tolerances to high osmolarity, oxidation, cell wall stress, high temperature and UV-B irradiation...
April 2015: Environmental Microbiology
Ayse Koca Caydasi, Yagmur Micoogullari, Bahtiyar Kurtulmus, Saravanan Palani, Gislene Pereira
In addition to their well-known role in microtubule organization, centrosomes function as signaling platforms and regulate cell cycle events. An important example of such a function is the spindle position checkpoint (SPOC) of budding yeast. SPOC is a surveillance mechanism that ensures alignment of the mitotic spindle along the cell polarity axis. Upon spindle misalignment, phosphorylation of the SPOC component Bfa1 by Kin4 kinase engages the SPOC by changing the centrosome localization of Bfa1 from asymmetric (one centrosome) to symmetric (both centrosomes)...
July 15, 2014: Molecular Biology of the Cell
Feng Zhang, Tammy Pracheil, Janet Thornton, Zhengchang Liu
Intracellular communication from the mitochondria to the nucleus is achieved via the retrograde response. In budding yeast, the retrograde response, also known as the RTG pathway, is regulated positively by Rtg1, Rtg2, Rtg3 and Grr1 and negatively by Mks1, Lst8 and two 14-3-3 proteins, Bmh1/2. Activation of retrograde signaling leads to activation of Rtg1/3, two basic helix-loop-helix leucine zipper transcription factors. Rtg1/3 activation requires Rtg2, a cytoplasmic protein with an N-terminal adenosine triphosphate (ATP) binding domain belonging to the actin/Hsp70/sugar kinase superfamily...
March 2013: Genes
Michael A Trembley, Hunter L Berrus, Jonathan R Whicher, Emily L Humphrey-Dixon
14-3-3 proteins are highly conserved and have been found in all eukaryotic organisms investigated. They are involved in many varied cellular processes, and interact with hundreds of other proteins. Among many other roles in cells, yeast 14-3-3 proteins have been implicated in rapamycin-mediated cell signaling. We determined the transcription profiles of bmh1 and bmh2 yeast after treatment with rapamycin. We found that, under these conditions, BMH1 and BMH2 are required for rapamycin-induced regulation of distinct, but overlapping sets of genes...
January 17, 2014: Bioscience Reports
Aymé Spor, Daniel J Kvitek, Thibault Nidelet, Juliette Martin, Judith Legrand, Christine Dillmann, Aurélie Bourgais, Dominique de Vienne, Gavin Sherlock, Delphine Sicard
Different organisms have independently and recurrently evolved similar phenotypic traits at different points throughout history. This phenotypic convergence may be caused by genotypic convergence and in addition, constrained by historical contingency. To investigate how convergence may be driven by selection in a particular environment and constrained by history, we analyzed nine life-history traits and four metabolic traits during an experimental evolution of six yeast strains in four different environments...
March 2014: Evolution; International Journal of Organic Evolution
Jan D van Gool, Tom P V M de Jong, Pauline Winkler-Seinstra, Tytti Tamminen-Möbius, Hildegard Lax, Herbert Hirche, Rien J M Nijman, Kelm Hjälmås, Ulf Jodal, Hannsjörg Bachmann, Piet Hoebeke, Johan Vande Walle, Joachim Misselwitz, Ulrike John, An Bael
OBJECTIVE: Functional urinary incontinence causes considerable morbidity in 8.4% of school-age children, mainly girls. To compare oxybutynin, placebo, and bladder training in overactive bladder (OAB), and cognitive treatment and pelvic floor training in dysfunctional voiding (DV), a multi-center controlled trial was designed, the European Bladder Dysfunction Study. METHODS: Seventy girls and 27 boys with clinically diagnosed OAB and urge incontinence were randomly allocated to placebo, oxybutynin, or bladder training (branch I), and 89 girls and 16 boys with clinically diagnosed DV to either cognitive treatment or pelvic floor training (branch II)...
June 2014: Neurourology and Urodynamics
Eva Macakova, Miroslava Kopecka, Zdenek Kukacka, Dana Veisova, Petr Novak, Petr Man, Tomas Obsil, Veronika Obsilova
BACKGROUND: Trehalases are highly conserved enzymes catalyzing the hydrolysis of trehalose in a wide range of organisms. The activity of yeast neutral trehalase Nth1 is regulated in a 14-3-3- and a calcium-dependent manner. The Bmh proteins (the yeast 14-3-3 isoforms) recognize phosphorylated Nth1 and enhance its enzymatic activity through an unknown mechanism. METHODS: To investigate the structural basis of interaction between Nth1 and Bmh1, we used hydrogen/deuterium exchange coupled to mass spectrometry, circular dichroism spectroscopy and homology modeling to identify structural changes occurring upon the complex formation...
October 2013: Biochimica et Biophysica Acta
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