The Novel Yeast PAS Kinase Rim15 Orchestrates G0-Associated Antioxidant Defense Mechanisms

Cameroni, Elisabetta; Hulo, Nicolas; Roosen, Johnny; Winderickx, Joris; Virgilio, Claudio De

doi:10.4161/cc.3.4.791

Cited by 152 publications

(188 citation statements)

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“…TORC1 regulates MSN2/4 by promoting their phophorylation and cytoplasmic accumulation, which may or may not (Santhanam et al, 2004) require cytoplasmic 14-3-3 anchor proteins. Following nutrient limitation, transcriptional activation by MSN2/4, and GIS1, a closely related transcription factor that activates expression of post-diauxic-shift (PDS) element-controlled genes, also requires the Ser/Thr protein kinase RIM15 (Reinders et al, 1998;Pedruzzi et al, 2003;Cameroni et al, 2004). Intriguingly, the nucleocytoplasmic distribution of RIM15 is also controlled by TORC1 in a 14-3-3-dependent fashion (Reinders et al, 1998;Pedruzzi et al, 2003;Wanke et al, 2005).…”

Section: Activity Of Stress-responsive Transcription Factorsmentioning

confidence: 99%

“…Intriguingly, the nucleocytoplasmic distribution of RIM15 is also controlled by TORC1 in a 14-3-3-dependent fashion (Reinders et al, 1998;Pedruzzi et al, 2003;Wanke et al, 2005). RIM15 is required to orchestrate key aspects of the G 0 programme although the mechanisms by which it influences MSN2/4 and GIS1 activity are not known (Cameroni et al, 2004;Swinnen et al, 2006). TORC1 prevents both the nuclear localization and stabilization of an additional transcription factor, IME1 (Colomina et al, 2003).…”

Section: Activity Of Stress-responsive Transcription Factorsmentioning

confidence: 99%

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Cell growth control: little eukaryotes make big contributions

2006

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The story of rapamycin is a pharmaceutical fairytale. Discovered as an antifungal activity in a soil sample collected on Easter Island, this macrocyclic lactone and its derivatives are now billion dollar drugs, used in, and being evaluated for, a number of clinical applications. Taking advantage of its antifungal property, the molecular Target Of Rapamycin, TOR, was first described in the budding yeast Saccharomyces cerevisiae. TORs encode large, Ser/Thr protein kinases that reside in two distinct, structurally and functionally conserved, multi-protein complexes. In yeast, these complexes coordinate many different aspects of cell growth. TOR complex 1, TORC1, promotes protein synthesis and other anabolic processes, while inhibiting macroautophagy and other catabolic and stress-response processes. TORC2 primarily regulates cell polarity, although additional readouts of this complex are beginning to be characterized. TORC1 appears to be activated by nutrient cues and inhibited by stresses and rapamycin; however, detailed mechanisms are not known. In contrast, TORC2 is insensitive to rapamycin and physiological regulators of this complex have yet to be defined. Given the unsurpassed resources available to yeast researchers, this simple eukaryote continues to contribute to our understanding of eukaryotic cell growth in general and TOR function in particular

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Section: Activity Of Stress-responsive Transcription Factorsmentioning

confidence: 99%

Section: Activity Of Stress-responsive Transcription Factorsmentioning

confidence: 99%

Cell growth control: little eukaryotes make big contributions

2006

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“…Although TPK/BCY1 was not upregulated in immobilized yeast, both RIM15 and MSN4 were (Fig. 4B), showing that immobilization per se activates these key stress response regulators (46,49). Two other zinc-finger proteins in this cluster, NRG2 and MIG2, are transcription factors that negatively regulate expression of glucose-repressible genes.…”

Section: Two-class Sam Reveals Immobilization-specific Changes In Genmentioning

confidence: 99%

Uncoupling reproduction from metabolism extends chronological lifespan in yeast

Nagarajan

Kruckeberg

Schmidt

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Studies of replicative and chronological lifespan in Saccharomyces cerevisiae have advanced understanding of longevity in all eukaryotes. Chronological lifespan in this species is defined as the agedependent viability of nondividing cells. To date this parameter has only been estimated under calorie restriction, mimicked by starvation. Because postmitotic cells in higher eukaryotes often do not starve, we developed a model yeast system to study cells as they age in the absence of calorie restriction. Yeast cells were encapsulated in a matrix consisting of calcium alginate to form ∼3 mm beads that were packed into bioreactors and fed ad libitum. Under these conditions cells ceased to divide, became heat shock and zymolyase resistant, yet retained high fermentative capacity. Over the course of 17 d, immobilized yeast cells maintained >95% viability, whereas the viability of starving, freely suspended (planktonic) cells decreased to <10%. Immobilized cells exhibited a stable pattern of gene expression that differed markedly from growing or starving planktonic cells, highly expressing genes in glycolysis, cell wall remodeling, and stress resistance, but decreasing transcription of genes in the tricarboxylic acid cycle, and genes that regulate the cell cycle, including master cyclins CDC28 and CLN1. Stress resistance transcription factor MSN4 and its upstream effector RIM15 are conspicuously up-regulated in the immobilized state, and an immobilized rim15 knockout strain fails to exhibit the long-lived, growth-arrested phenotype, suggesting that altered regulation of the Rim15-mediated nutrient-sensing pathway plays an important role in extending yeast chronological lifespan under calorie-unrestricted conditions. cell longevity | Ca-alginate encapsulation U nicellular microbes senesce and die (for reviews, see refs.

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“…The mechanism of TOR-dependent cytoplasmic retention of Msn2/4 and Rim 15 may involve inhibitory binding of the transcription factor complex by the 14-3-3 proteins Bmh1 and Bmh2 [99,101]. Rim15, when translocated to the nucleus, promotes activation of the Msn2/4 and Gis1 transcription factors [102,103]. Among the targets of Msn2/4 and Gis1 are components of oxidative defence pathways including superoxide dismutase.…”

Section: Introductionmentioning

confidence: 99%

TOR and ageing: a complex pathway for a complex process

McCormick

Tsai

Kennedy

2011

Phil. Trans. R. Soc. B

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Studies in invertebrate model organisms have led to a wealth of knowledge concerning the ageing process. But which of these discoveries will apply to ageing in humans? Recently, an assessment of the degree of conservation of ageing pathways between two of the leading invertebrate model organisms, Saccharomyces cerevisiae and Caenorhabditis elegans, was completed. The results (i) quantitatively indicated that pathways were conserved between evolutionarily disparate invertebrate species and (ii) emphasized the importance of the TOR kinase pathway in ageing. With recent findings that deletion of the mTOR substrate S6K1 or exposure of mice to the mTOR inhibitor rapamycin result in lifespan extension, mTOR signalling has become a major focus of ageing research. Here, we address downstream targets of mTOR signalling and their possible links to ageing. We also briefly cover other ageing genes identified by comparing worms and yeast, addressing the likelihood that their mammalian counterparts will affect longevity.

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The Novel Yeast PAS Kinase Rim15 Orchestrates G0-Associated Antioxidant Defense Mechanisms

Cited by 152 publications

References 50 publications

Cell growth control: little eukaryotes make big contributions

Cell growth control: little eukaryotes make big contributions

Uncoupling reproduction from metabolism extends chronological lifespan in yeast

TOR and ageing: a complex pathway for a complex process

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