A Functional Analysis Reveals Dependence on the Anaphase-Promoting Complex for Prolonged Life Span in Yeast

Harkness, Troy A. A.; Shea, Kyla A.; Legrand, Charmaine; Brahmania, Mayur; Davies, Gerald F.

doi:10.1534/genetics.104.027771

Cited by 43 publications

(74 citation statements)

References 90 publications

(28 reference statements)

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“…Hcm1 is tightly linked to Fkh1/2 activity as it transcribes FKH1 and FKH2 during late S phase (70). We have shown previously that the yeast anaphase-promoting complex is a crucial player in maintaining normal life span and stress response and that Snf1 and Fkh1/2 are involved in these activities (16,71). Although Snf1 interacts physically with Hcm1, there is no indication in the literature that Snf1 interacts with Fkh1/2.…”

Section: Discussionmentioning

confidence: 99%

“…RLS measures the mitotic capacity of yeast cells by determining the number of daughter cells a single mother can produce (50). We previously demonstrated that Snf1 plays a role in extending yeast RLS via Mig1 inhibition (16), and others have shown that RLS is reduced when the SNF1 kinase Sip1 ␤ subunit is deleted (15,51). Here, we show that under minor nutrient stress conditions (growth on 2% glucose dropout media), snf1⌬ cells have an obvious decrease in RLS when compared with plasmidborne Snf1-HA (16 versus 19 generations; Fig.…”

Section: Activation Of the Snf1mentioning

confidence: 99%

“…The SNF1 kinase is important for the yeast stress response (12) and facilitates adaptation to glucose limitation, regulating the activity of metabolic enzymes and the transcription of metabolic genes. In addition to metabolic effects, this family of kinases has also been found to protect against oxidative stress and to impact the life span of model systems (13)(14)(15)(16). As an enzyme complex that must efficiently respond to metabolic signals, its activity incorporates the rapid and reversible phosphorylation of its catalytic ␣ subunit by well defined upstream kinases (Pak1, Elm1, and Tos3) (17) and phosphatases, with a major contributor being protein phosphatase I, Glc7-Reg1 (18 -21).…”

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confidence: 99%

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The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

Jiao¹,

Postnikoff²,

Harkness³

et al. 2015

Journal of Biological Chemistry

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Background:The UBA domain in the AMP kinase family is poorly defined. Results: This motif restrains kinase activity, resulting in decreased life span and oxidative stress resistance. Conclusion: This inhibitory domain has defined influences with FOXOs on stress and aging. Significance: The overactive kinase created by UBA mutations has positive stress resistance and aging influences that may translate to human metabolic benefits.

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Section: Discussionmentioning

confidence: 99%

Section: Activation Of the Snf1mentioning

confidence: 99%

mentioning

confidence: 99%

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The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

Jiao¹,

Postnikoff²,

Harkness³

et al. 2015

Journal of Biological Chemistry

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“…Besides its role in the response to glucose limitation, Snf1 has also been implicated in several other processes, including aging, thermotolerance, peroxisome biogenesis, filamentation, invasive growth, biofilm formation, meiosis, and (like Glc7) sporulation (8,45,137,196,197,297,401). Clearly more work is needed before we will fully understand the respective relationships between the distinct forms of the Snf1 kinase complex and each of these regulatory mechanisms.…”

Section: Snf1-mediated Signal Transduction In Glucose Repression and mentioning

confidence: 99%

Glucose Signaling in Saccharomyces cerevisiae

Santangelo

2006

Microbiol Mol Biol Rev

476

481

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SUMMARY Eukaryotic cells possess an exquisitely interwoven and fine-tuned series of signal transduction mechanisms with which to sense and respond to the ubiquitous fermentable carbon source glucose. The budding yeast Saccharomyces cerevisiae has proven to be a fertile model system with which to identify glucose signaling factors, determine the relevant functional and physical interrelationships, and characterize the corresponding metabolic, transcriptomic, and proteomic readouts. The early events in glucose signaling appear to require both extracellular sensing by transmembrane proteins and intracellular sensing by G proteins. Intermediate steps involve cAMP-dependent stimulation of protein kinase A (PKA) as well as one or more redundant PKA-independent pathways. The final steps are mediated by a relatively small collection of transcriptional regulators that collaborate closely to maximize the cellular rates of energy generation and growth. Understanding the nuclear events in this process may necessitate the further elaboration of a new model for eukaryotic gene regulation, called “reverse recruitment.” An essential feature of this idea is that fine-structure mapping of nuclear architecture will be required to understand the reception of regulatory signals that emanate from the plasma membrane and cytoplasm. Completion of this task should result in a much improved understanding of eukaryotic growth, differentiation, and carcinogenesis.

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“…It is the catalytic subunit of the heterotrimeric SNF1 complex, which also contains the coactivating ␥ subunit Snf4 and 1 of 3 ß subunits (Sip2 in our network) that influence subcellular localization of the complex (21). Many genes in the Snf1 network are known to affect RLS when perturbed, including Snf1, Sip2, Snf4 (22), Mig1 (23), and Hxk2 (5,8). In a glucose-rich environment, the transcription factor (TF) Mig1 represses alternative carbon source metabolism and gluconeogenesis gene expression, including enzyme SUC2 and TF CAT8 (7,9,21).…”

mentioning

confidence: 99%

A network biology approach to aging in yeast

Lorenz

Cantor

Collins

2009

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

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In this study, a reverse-engineering strategy was used to infer and analyze the structure and function of an aging and glucose repressed gene regulatory network in the budding yeast Saccharomyces cerevisiae. The method uses transcriptional perturbations to model the functional interactions between genes as a system of first-order ordinary differential equations. The resulting network model correctly identified the known interactions of key regulators in a 10-gene network from the Snf1 signaling pathway, which is required for expression of glucose-repressed genes upon calorie restriction. The majority of interactions predicted by the network model were confirmed using promoter-reporter gene fusions in gene-deletion mutants and chromatin immunoprecipitation experiments, revealing a more complex network architecture than previously appreciated. The reverse-engineered network model also predicted an unexpected role for transcriptional regulation of the SNF1 gene by hexose kinase enzyme/transcriptional repressor Hxk2, Mediator subunit Med8, and transcriptional repressor Mig1. These interactions were validated experimentally and used to design new experiments demonstrating Snf1 and its transcriptional regulators Hxk2 and Mig1 as modulators of chronological lifespan. This work demonstrates the value of using network inference methods to identify and characterize the regulators of complex phenotypes, such as aging.chronological aging ͉ gene networks ͉ Snf1 pathway ͉ systems biology

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A Functional Analysis Reveals Dependence on the Anaphase-Promoting Complex for Prolonged Life Span in Yeast

Cited by 43 publications

References 90 publications

The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

The SNF1 Kinase Ubiquitin-associated Domain Restrains Its Activation, Activity, and the Yeast Life Span

Glucose Signaling in Saccharomyces cerevisiae

A network biology approach to aging in yeast

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