Eukaryotic Cell Size Control and Its Relation to Biosynthesis and Senescence

Annual Review of Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 38(1), P. 291 - 319

Published: May 14, 2022

The most fundamental feature of cellular form is size, which sets the scale all cell biological processes. Growth, form, and function are necessarily linked in biology, but we often do not understand underlying molecular mechanisms nor their specific functions. Here, review progress toward determining that regulate size yeast, animals, plants, as well understanding regulation. It has become increasingly clear mechanism regulation deeply intertwined with basic biosynthesis, how biosynthesis can be scaled (or not) proportion to size. Finally, highlight recent findings causally linking aberrant senescence implications for cancer therapies.

Language: Английский

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Cell Cycle-Dependent Transcription: The Cyclin Dependent Kinase Cdk1 Is a Direct Regulator of Basal Transcription Machineries

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1293 - 1293

Published: Jan. 24, 2022

The cyclin-dependent kinase Cdk1 is best known for its function as master regulator of the cell cycle. It phosphorylates several key proteins to control progression through different phases However, studies conducted decades ago with mammalian cells revealed that also directly regulates basal transcription machinery, most notably RNA polymerase II. More recent in budding yeast Saccharomyces cerevisiae have revisited this and controls III activity. These provided novel insight into physiological relevance process. For instance, cycle-stage-dependent activity these complexes may be important meeting increased demand various involved housekeeping, metabolism, protein synthesis. Recent work indicates direct regulation II machinery promotes cycle entry. Here, we provide an overview by Cdk1, hypothesize original primordial cell-cycle CDK was regulate RNAPII it later evolved specialized kinases govern aspects

Language: Английский

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Cyclin‐dependent kinases: Masters of the eukaryotic universe

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2023, Volume and Issue: 15(1)

Published: Sept. 17, 2023

Abstract A family of structurally related cyclin‐dependent protein kinases (CDKs) drives many aspects eukaryotic cell function. Much the literature in this area has considered individual members to act primarily either as regulators cycle, context which CDKs were first discovered, or transcription. Until recently, CDK7 was only clear example a CDK that functions both processes. However, new data points several “cell‐cycle” having important roles transcription and some “transcriptional” cycle‐related targets. For example, novel have been demonstrated for archetypal cycle regulator CDK1. The increasing evidence overlap between these two types suggests they might play critical role coordinating Here we review canonical cell‐cycle transcriptional CDKs, provide an update on how collaborate perform cellular functions. We also brief overview dysregulation contributes carcinogenesis, possible treatment avenues. This article is categorized under: RNA Interactions with Proteins Other Molecules > RNA‐Protein Complexes Processing 3′ End Splicing Regulation/Alternative

Language: Английский

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The CDK9-SPT5 axis in control of transcription elongation by RNAPII

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: unknown, P. 168746 - 168746

Published: Aug. 1, 2024

Language: Английский

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The CDK Pho85 inhibits Whi7 Start repressor to promote cell cycle entry in budding yeast

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(2), P. 745 - 769

Published: Jan. 17, 2024

Abstract Pho85 is a multifunctional CDK that signals to the cell when environmental conditions are favorable. It has been connected cycle control, mainly in Start where it promotes G1/S transition. Here we describe repressor Whi7 key target of regulation entry. The phosphorylation by inhibits and explains most contribution activation Start. Mechanistically, downregulates protein levels through control stability WHI7 gene transcription. also restrains intrinsic ability associate with promoters. Furthermore, although Whi5 main normal cycling cells, absence Pho85, becomes major leading G1 arrest. Overall, our results reveal novel mechanism which at multiple levels, may confer functional specialization connect response adverse control.

Language: Английский

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Extending the G1 phase improves the production of lipophilic compounds in yeast by boosting enzyme expression and increasing cell size

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(47)

Published: Nov. 13, 2024

Cell phase engineering can significantly impact protein synthesis and cell size, potentially enhancing the production of lipophilic products. This study investigated G1 extension on resource allocation, metabolic functions, unfolded response (UPR) in yeast, along with potential for compounds. In brief, regulation was achieved by deleting

Language: Английский

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What programs the size of animal cells?

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Nov. 1, 2022

The human body is programmed with definite quantities, magnitudes, and proportions. At the microscopic level, such sizes manifest in individual cells - different cell types are characterized by distinct whereas of same type highly uniform size. How do a population maintain uniformity size, how changes target size programmed? A convergence recent historical studies suggest just as thermostat maintains room temperature proliferating animal similarly maintained homeostatic mechanisms. In this review, we first summarize old new literature on existence checkpoints, then discuss additional advances study homeostasis that involve feedback regulation cellular growth rate. We further progress molecules underlie checkpoints mechanisms specify setpoints. Lastly, less-well explored teleological question: why does matter what functional importance control?

Language: Английский

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CDK signaling via nonconventional CDK phosphorylation sites

Molecular Biology of the Cell, Journal Year: 2023, Volume and Issue: 34(12)

Published: Oct. 31, 2023

Since the discovery of cyclin-dependent kinases (CDKs), it has been perceived as a dogma that CDK signaling in cell cycle is mediated via targeting consensus sites: optimal and minimal motifs S/T-P-x-K/R S/T-P, respectively. However, more recent evidence suggests often phosphorylation events regulatory importance are nonconventional sites lack required +1Pro site motif. In these cases, loss specificity seems to be compensated distant docking interactions facilitated by 1) phosphorylated priming binding phospho-adaptor Cks1 and/or 2) cyclin-specific Short Linear Motifs (SLiMs) substrates. This

Language: Английский

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STING signaling in inflammaging: a new target against musculoskeletal diseases

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 10, 2023

Stimulator of Interferon Gene (STING) is a critical signaling linker protein that plays crucial role in the intrinsic immune response, particularly cytoplasmic DNA-mediated response both pathogens and hosts. It also involved various processes vivo . The musculoskeletal system provides humans with morphology, support, stability, movement. However, its aging can result diseases negatively impact people’s lives. While many studies have reported cellular leading cause disorders, it offers insight into potential treatments. Under pathological conditions, senescent osteoblasts, chondrocytes, myeloid cells, muscle fibers exhibit persistent senescence-associated secretory phenotype (SASP), metabolic disturbances, cell cycle arrest, which are closely linked to abnormal STING activation. accumulation DNA due chromatin escape from nucleus following damage or telomere shortening activates cGAS-STING pathway. Moreover, activation mitochondrial dysfunction, epigenetic modifications, impaired degradation. upregulates SASP autophagy directly indirectly promotes arrest. Thus, may be onset development age-related disorders represents therapeutic target. In recent years, modulators been developed used study disorders. Therefore, this paper summarizes effects on at molecular level current understanding mechanisms endogenous active ligand production accumulation. We discuss relationship between some STING, as well status modulator development.

Language: Английский

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Dual regulation of the levels and function of Start transcriptional repressors drives G1 arrest in response to cell wall stress

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 16, 2025

Many different stress signaling pathways converge in a common response: slowdown or arrest cell cycle the G1 phase. The G1/S transition (called Start budding yeast) is key checkpoint controlled by positive and negative regulators. Among them, Whi7 Whi5 are transcriptional repressors of program, yeast functional homologs Retinoblastoma family proteins mammalian cells. Under standard conditions, plays lesser role than inhibition. However, under wall stress, induced more important control. In this work, we investigated hallmarks Whi5, which determine their strength as inhibitors stress. response Saccharomyces cerevisiae to Calcofluor White was characterize regulation function To control protein levels, used dose-dependent β-estradiol-induced expression auxin-induced degron fusions. We also performed Chromatin Immunoprecipitation assays investigate association with promoters scored re-entry using microscopy assays. found that promoted specific upregulation repressor. First, although increases not only determinant behind promoting arrest. Indeed, artificial induction at same level resulted lower block. Second, specifically recruited SBF-target promoters, independent increase its levels stage. Finally, instability further increased during degradation triggered advanced re-entry. Here, show enhances Importantly, identified new Whi7-specific regulatory mechanisms do operate Our results indicate cells may benefit from stress-specific ensure stress-induced rapid be particularly resume upon adaptation.

Language: Английский

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