scholarly journals Mechanisms of expression and translocation of major fission yeast glucose transporters regulated by CaMKK/phosphatases, nuclear shuttling, and TOR

2015 ◽  
Vol 26 (2) ◽  
pp. 373-386 ◽  
Author(s):  
Shigeaki Saitoh ◽  
Ayaka Mori ◽  
Lisa Uehara ◽  
Fumie Masuda ◽  
Saeko Soejima ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Glucose Homeostasis ◽  
Molecular Mechanisms ◽  
Transcriptional Regulator ◽  
Hexose Transporter ◽  
Evolutionarily Conserved ◽  
Hexose Transporters ◽  
Extracellular Glucose ◽  
Nuclear Shuttling ◽  
Multicellular Organisms

Hexose transporters are required for cellular glucose uptake; thus they play a pivotal role in glucose homeostasis in multicellular organisms. Using fission yeast, we explored hexose transporter regulation in response to extracellular glucose concentrations. The high-affinity transporter Ght5 is regulated with regard to transcription and localization, much like the human GLUT transporters, which are implicated in diabetes. When restricted to a glucose concentration equivalent to that of human blood, the fission yeast transcriptional regulator Scr1, which represses Ght5 transcription in the presence of high glucose, is displaced from the nucleus. Its displacement is dependent on Ca2+/calmodulin-dependent kinase kinase, Ssp1, and Sds23 inhibition of PP2A/PP6-like protein phosphatases. Newly synthesized Ght5 locates preferentially at the cell tips with the aid of the target of rapamycin (TOR) complex 2 signaling. These results clarify the evolutionarily conserved molecular mechanisms underlying glucose homeostasis, which are essential for preventing hyperglycemia in humans.

scholarly journals Reciprocal Nuclear Shuttling of Two Antagonizing Zn Finger Proteins Modulates Tup Family Corepressor Function To Repress Chromatin Remodeling

2006 ◽  
Vol 5 (12) ◽  
pp. 1980-1989 ◽  
Author(s):  
Kouji Hirota ◽  
Charles S. Hoffman ◽  
Kunihiro Ohta
Keyword(s):  
Chromatin Remodeling ◽  
Transcriptional Repression ◽  
Molecular Mechanisms ◽  
Glucose Repression ◽  
Regulatory Elements ◽  
Initial Stage ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
Nuclear Shuttling

ABSTRACT The Schizosaccharomyces pombe global corepressors Tup11 and Tup12, which are orthologs of Saccharomyces cerevisiae Tup1, are involved in glucose-dependent transcriptional repression and chromatin alteration of the fbp1 + gene. The fbp1 + promoter contains two regulatory elements, UAS1 and UAS2, one of which (UAS2) serves as a binding site for two antagonizing C2H2 Zn finger transcription factors, the Rst2 activator and the Scr1 repressor. In this study, we analyzed the role of Tup proteins and Scr1 in chromatin remodeling at fbp1 + during glucose repression. We found that Scr1, cooperating with Tup11 and Tup12, functions to maintain the chromatin of the fbp1 + promoter in a transcriptionally inactive state under glucose-rich conditions. Consistent with this notion, Scr1 is quickly exported from the nucleus to the cytoplasm at the initial stage of derepression, immediately after glucose starvation, at which time Rst2 is known to be imported into the nucleus. In addition, chromatin immunoprecipitation assays revealed a switching of Scr1 to Rst2 bound at UAS2 during glucose derepression. On the other hand, Tup11 and Tup12 persist in the nucleus and bind to the fbp1 + promoter under both derepressed and repressed conditions. These observations suggest that Tup1-like proteins recruited to the fbp1 + promoter are controlled by either of two antagonizing C2H2 Zn finger proteins. We propose that the actions of Tup11 and Tup12 are regulated by reciprocal nuclear shuttling of the two antagonizing Zn finger proteins in response to the extracellular glucose concentration. This notion provides new insights into the molecular mechanisms of the Tup family corepressors in gene regulation.

scholarly journals Fission Yeast TORC2 Signaling Pathway Ensures Cell Proliferation under Glucose-Limited, Nitrogen-Replete Conditions

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1465
Author(s):  
Yusuke Toyoda ◽  
Shigeaki Saitoh
Keyword(s):  
Cell Proliferation ◽  
Cell Surface ◽  
Fission Yeast ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Nitrogen Sources ◽  
Biochemical Processes ◽  
Evolutionarily Conserved ◽  
Surface Localization ◽  
Cell Surface Localization

Target of rapamycin (TOR) kinases form two distinct complexes, TORC1 and TORC2, which are evolutionarily conserved among eukaryotes. These complexes control intracellular biochemical processes in response to changes in extracellular nutrient conditions. Previous studies using the fission yeast, Schizosaccharomyces pombe, showed that the TORC2 signaling pathway, which is essential for cell proliferation under glucose-limited conditions, ensures cell-surface localization of a high-affinity hexose transporter, Ght5, by downregulating its endocytosis. The TORC2 signaling pathway retains Ght5 on the cell surface, depending on the presence of nitrogen sources in medium. Ght5 is transported to vacuoles upon nitrogen starvation. In this review, we discuss the molecular mechanisms underlying this regulation to cope with nutritional stress, a response which may be conserved from yeasts to mammals.

A snapshot of Snf2 enzymes in fission yeast

2013 ◽  
Vol 41 (6) ◽  
pp. 1640-1647 ◽  
Author(s):  
Punit Prasad ◽  
Karl Ekwall
Keyword(s):  
Gene Expression ◽  
Fission Yeast ◽  
Molecular Mechanisms ◽  
Dna Recombination ◽  
Chromatin Remodelling ◽  
Present Review ◽  
Dependent Manner ◽  
Evolutionarily Conserved ◽  
Eukaryotic Chromatin ◽  
Heterochromatin Structure

Eukaryotic chromatin is remodelled by the evolutionarily conserved Snf2 family of enzymes in an ATP-dependent manner. Several Snf2 enzymes are part of CRCs (chromatin remodelling complexes). In the present review we focus our attention on the functions of Snf2 enzymes and CRCs in fission yeast. We discuss their molecular mechanisms and roles and in regulating gene expression, DNA recombination, euchromatin and heterochromatin structure.

Apoptosis and development

2003 ◽  
Vol 39 ◽  
pp. 11-24 ◽  
Author(s):  
Justin V McCarthy
Keyword(s):  
Drosophila Melanogaster ◽  
Mammalian Cells ◽  
Cell Number ◽  
Model Organisms ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
Apoptotic Pathway ◽  
Genetic Pathways ◽  
Evolutionarily Conserved ◽  
Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

scholarly journals YWHAZ interacts with DAAM1 to promote cell migration in breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jie Mei ◽  
Yan Liu ◽  
Xinqian Yu ◽  
Leiyu Hao ◽  
Tao Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Transcriptional Regulator ◽  
Expression Levels ◽  
Functional Roles ◽  
Normal Tissues ◽  
Rhoa Activation ◽  
Promote Cell Migration

AbstractDishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)–DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ–DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ–DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.

Hexose transporter expression in rat small intestine: effect of diet on diurnal variations

1996 ◽  
Vol 271 (1) ◽  
pp. G211-G216 ◽  
Author(s):  
C. P. Corpe ◽  
C. F. Burant
Keyword(s):  
Daily Variation ◽  
Control Diet ◽  
Diurnal Variations ◽  
Mrna Levels ◽  
Hexose Transporter ◽  
Diurnal Pattern ◽  
Protein Levels ◽  
Feeding Study ◽  
Hexose Transporters ◽  
Transporter Expression

In rodents, a number of intestinal digestive and absorptive processes demonstrate a diurnal pattern of activity. To investigate if the jejunal hexose transporters are regulated in such a diurnal fashion, the levels for the glucose and fructose transporter mRNA and proteins were determined at 6-h intervals over a 24-h control fed period. SGLT-1, GLUT-2, and GLUT-5 mRNA levels increased between two- and eightfold before the onset of peak feeding. GLUT-5 protein levels also varied in a diurnal fashion but were out of phase with the observed changes in GLUT-5 mRNA levels. In contrast, GLUT-2 protein levels remained relatively constant during the control fed 24-h period. The effect of dietary manipulations on the observed diurnal variation was also investigated. After only 3 h of feeding a 60% fructose-enriched diet, the levels of GLUT-5 mRNA and protein were significantly elevated. GLUT-5 mRNA and protein levels remained elevated relative to the level of control diet-fed animals over the ensuing 24 h and during the 7th day of fructose feeding. Exposure to elevated levels of fructose had no significant effect on the diurnal pattern of GLUT-2 and SGLT-1 mRNA. In contrast, GLUT-2 protein was rapidly downregulated during the length of the fructose feeding study. In conclusion, the data demonstrate a normal daily variation in the level of hexose transporter expression that can be rapidly modulated by diet.

scholarly journals A concise review on advances in development of small molecule anti-inflammatory therapeutics emphasising AMPK: An emerging target

2016 ◽  
Vol 29 (4) ◽  
pp. 562-571 ◽  
Author(s):  
Chethan Gejjalagere Honnappa ◽  
Unnikrishnan Mazhuvancherry Kesavan
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Cyclooxygenase Inhibitors ◽  
Evolutionarily Conserved ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Acid Pathway ◽  
Clinical Trial Results ◽  
Amp Activated Protein Kinase

Inflammatory diseases are complex, multi-factorial outcomes of evolutionarily conserved tissue repair processes. For decades, non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors, the primary drugs of choice for the management of inflammatory diseases, addressed individual targets in the arachidonic acid pathway. Unsatisfactory safety and efficacy profiles of the above have necessitated the development of multi-target agents to treat complex inflammatory diseases. Current anti-inflammatory therapies still fall short of clinical needs and the clinical trial results of multi-target therapeutics are anticipated. Additionally, new drug targets are emerging with improved understanding of molecular mechanisms controlling the pathophysiology of inflammation. This review presents an outline of small molecules and drug targets in anti-inflammatory therapeutics with a summary of a newly identified target AMP-activated protein kinase, which constitutes a novel therapeutic pathway in inflammatory pathology.

scholarly journals Current and Emerging Biomarkers of Cell Death in Human Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kongning Li ◽  
Deng Wu ◽  
Xi Chen ◽  
Ting Zhang ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Research Area ◽  
Human Diseases ◽  
Mitotic Catastrophe ◽  
Regulated Necrosis ◽  
Early Diagnose ◽  
Multicellular Organisms ◽  
The Relationship ◽  
Made In

Cell death is a critical biological process, serving many important functions within multicellular organisms. Aberrations in cell death can contribute to the pathology of human diseases. Significant progress made in the research area enormously speeds up our understanding of the biochemical and molecular mechanisms of cell death. According to the distinct morphological and biochemical characteristics, cell death can be triggered by extrinsic or intrinsic apoptosis, regulated necrosis, autophagic cell death, and mitotic catastrophe. Nevertheless, the realization that all of these efforts seek to pursue an effective treatment and cure for the disease has spurred a significant interest in the development of promising biomarkers of cell death to early diagnose disease and accurately predict disease progression and outcome. In this review, we summarize recent knowledge about cell death, survey current and emerging biomarkers of cell death, and discuss the relationship with human diseases.

scholarly journals Circadian clock regulation of the glycogen synthase (gsn) gene by WCC is critical for rhythmic glycogen metabolism inNeurospora crassa

2019 ◽  
Vol 116 (21) ◽  
pp. 10435-10440 ◽  
Author(s):  
Mokryun Baek ◽  
Stela Virgilio ◽  
Teresa M. Lamb ◽  
Oneida Ibarra ◽  
Juvana Moreira Andrade ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Glucose Homeostasis ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Cellular Functions ◽  
Glycogen Accumulation ◽  
Homeostatic Process ◽  
Allosteric Control ◽  
Clock Component

Circadian clocks generate rhythms in cellular functions, including metabolism, to align biological processes with the 24-hour environment. Disruption of this alignment by shift work alters glucose homeostasis. Glucose homeostasis depends on signaling and allosteric control; however, the molecular mechanisms linking the clock to glucose homeostasis remain largely unknown. We investigated the molecular links between the clock and glycogen metabolism, a conserved glucose homeostatic process, inNeurospora crassa. We find that glycogen synthase (gsn) mRNA, glycogen phosphorylase (gpn) mRNA, and glycogen levels, accumulate with a daily rhythm controlled by the circadian clock. Because the synthase and phosphorylase are critical to homeostasis, their roles in generating glycogen rhythms were investigated. We demonstrate that whilegsnwas necessary for glycogen production, constitutivegsnexpression resulted in high and arrhythmic glycogen levels, and deletion ofgpnabolishedgsnmRNA rhythms and rhythmic glycogen accumulation. Furthermore, we show thatgsnpromoter activity is rhythmic and is directly controlled by core clock component white collar complex (WCC). We also discovered that WCC-regulated transcription factors, VOS-1 and CSP-1, modulate the phase and amplitude of rhythmicgsnmRNA, and these changes are similarly reflected in glycogen oscillations. Together, these data indicate the importance of clock-regulatedgsntranscription over signaling or allosteric control of glycogen rhythms, a mechanism that is potentially conserved in mammals and critical to metabolic homeostasis.

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