Publications by authors named "Michael Polymenis"

Cells adjust their proliferation in response to extrinsic factors and nutrients. Such inputs must reach the cell cycle machinery to ensure proper cell proliferation. This minireview focuses on evidence suggesting that phosphorylating the T-loop domain of cyclin-dependent kinases may be a critical and conserved conduit for these external signals.

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Effective dietary strategies and interventions for monitoring dietary exposures require accurate and noninvasive methods to understand how diet modulates health and risk of obesity; advances in technology are transforming the landscape and enabling more specific tailored approaches to nutritional guidance. This study explores the use of Raman spectroscopy (RS), a noninvasive and nondestructive analytical technique, to identify changes in the mice skin in response to constant dietary exposures. We found that RS is highly accurate to determine body composition as a result of habitual dietary patterns, specifically Vegan, Typical American, and Ketogenic diets, all very common in the US context.

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Proteins are the principal macromolecular constituent of proliferating cells, and protein synthesis is viewed as a primary metric of cell growth. While there are celebrated examples of proteins whose levels are periodic in the cell cycle (e.g.

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Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low-folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms.

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Protein synthesis underpins cell growth and controls when cells commit to a new round of cell division at a point in late G1 of the cell cycle called Start. Passage through Start also coincides with the duplication of the microtubule-organizing centers, the yeast spindle pole bodies, which will form the 2 poles of the mitotic spindle that segregates the chromosomes in mitosis. The conserved Mps1p kinase governs the duplication of the spindle pole body (SPB) in Saccharomyces cerevisiae.

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Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms.

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Profiling the repertoire of proteins associated with a given mRNA during the cell cycle is unstudied. Furthermore, it is easier to ask and answer what mRNAs a specific protein might bind to than the other way around. Here, we implemented an RNA-centric proximity labeling technology at different points in the cell cycle in highly synchronous yeast cultures.

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How cells coordinate their metabolism with division determines the rate of cell proliferation. Dynamic patterns of metabolite synthesis during the cell cycle are unexplored. We report the first isotope tracing analysis in synchronous, growing budding yeast cells.

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Enzymes of one-carbon (1C) metabolism play pivotal roles in proliferating cells. They are involved in the metabolism of amino acids, nucleotides, and lipids and the supply of all cellular methylations. However, there is limited information about how these enzymes are regulated during cell division and how cell cycle kinetics are affected in several loss-of-function mutants of 1C metabolism.

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Proteins that bind to each mRNA may affect the latter's abundance and location in the cell and how well ribosomes will translate that mRNA into a protein. Hence, mRNA-binding proteins (mRBPs) represent obvious control points in gene expression. Surprisingly, little is known about mRBPs and cell-cycle progression.

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There is interest in admission criteria that predict future success in biomedical graduate school programs, but identifying predictors of PhD attainment is inherently complex. In particular, high noncompletion rates of PhD programs have long been recognized as a major crisis. Here, we present a quantitative analysis of the PhD students enrolled in the Department of Biochemistry and Biophysics at Texas A&M University between 1980 and 2010.

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Continuously dividing cells coordinate their growth and division. How fast cells grow in mass determines how fast they will multiply. Yet, there are few, if any, examples of a metabolic pathway that actively drives a cell cycle event instead of just being required for it.

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Article Synopsis
  • Caloric restriction (CR) is linked to increased lifespan, but the specific molecular mechanisms behind this phenomenon are not fully understood, particularly in the context of glucose restriction (GR) in yeast.
  • Through techniques like ribosome profiling and RNA-seq, researchers found that GR decreases methionine levels by down-regulating related enzymes and transporters, which is essential for the observed lifespan extension.
  • Additionally, supplementing methionine negates the lifespan benefits from GR, suggesting a significant connection between methionine levels and cellular growth regulation in response to nutrients.
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Ribosomal proteins are highly conserved, many universally so among organisms. All ribosomal proteins are structural parts of the same molecular machine, the ribosome. However, when ribosomal proteins are mutated individually, they often lead to distinct and intriguing phenotypes, including specific human pathologies.

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A long-standing problem is how cells that lack one of the highly similar ribosomal proteins (RPs) often display distinct phenotypes. Yeast and other organisms live longer when they lack specific ribosomal proteins, especially of the large 60S subunit of the ribosome. However, longevity is neither associated with the generation time of RP deletion mutants nor with bulk inhibition of protein synthesis.

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A long-standing effort in biology is to precisely define and group phenotypes that characterize a biological process, and the genes that underpin them. In and other organisms, functional screens have generated rich lists of phenotypes associated with individual genes. However, it is often challenging to identify sets of phenotypes and genes that are most closely associated with a given biological process.

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Establishing the pattern of abundance of molecules of interest during cell division has been a long-standing goal of cell cycle studies. Here, for the first time in any system, we present experiment-matched datasets of the levels of RNAs, proteins, metabolites, and lipids from unarrested, growing, and synchronously dividing yeast cells. Overall, transcript and protein levels were correlated, but specific processes that appeared to change at the RNA level (e.

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The question of what determines whether cells are big or small has been the focus of many studies because it is thought that such determinants underpin the coupling of cell growth with cell division. In contrast, what determines the overall pattern of how cell size is distributed within a population of wild type or mutant cells has received little attention. Knowing how cell size varies around a characteristic pattern could shed light on the processes that generate such a pattern and provide a criterion to identify its genetic basis.

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The longer cells stay in particular phases of the cell cycle, the longer it will take these cell populations to increase. However, the above qualitative description has very little predictive value, unless it can be codified mathematically. A quantitative relation that defines the population doubling time (T) as a function of the time eukaryotic cells spend in specific cell cycle phases would be instrumental for estimating rates of cell proliferation and for evaluating introduced perturbations.

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Article Synopsis
  • Kes1/Osh4, part of the oxysterol binding protein-related superfamily, is crucial for controlling cell-cycle activities, specifically inhibiting the G/S transition in nutrient-poor conditions and promoting aging.* -
  • This regulation relies on the kinase Rim15 and counteracts the actions of Sec14, indicating a complex interaction independent of their membrane-trafficking roles.* -
  • The study suggests that Kes1 acts as a target for the NuA4 acetyltransferase, linking lipid signaling with cell-cycle control and proposing that ORPs may function like tumor suppressors in this process.*
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The varied nature of human cancers is recapitulated, at least to some extent, in the diverse NCI-60 panel of human cancer cell lines. Here, I used a basic, continuous variable of proliferating cells, their doubling time, to stratify the proteome across the NCI-60 cell lines. Among >7000 proteins quantified in the NCI-60 panel previously, the levels of 84 proteins increase in cells that proliferate slowly.

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Usually, cells balance their growth with their division. Coordinating growth inputs with cell division ensures the proper timing of division when sufficient cell material is available and affects the overall rate of cell proliferation. At a very fundamental level, cellular replicative lifespan-defined as the number of times a cell can divide, is a manifestation of cell cycle control.

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Understanding the causes and consequences of dynamic changes in the abundance and activity of cellular components during cell division is what most cell cycle studies are about. Here we focus on control of gene expression in the cell cycle at the level of translation. The advent of deep sequencing methodologies led to technologies that quantify the levels of all mRNAs that are bound by ribosomes and engaged in translation in the cell (Ingolia et al.

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