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.

scholarly journals Alp7-Mto1 and Alp14 synergize to promote interphase microtubule regrowth from the nuclear envelope

2019 ◽  
Vol 11 (11) ◽  
pp. 944-955 ◽  
Author(s):  
Wenyue Liu ◽  
Fan Zheng ◽  
Yucai Wang ◽  
Chuanhai Fu
Keyword(s):  
Nuclear Envelope ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Microtubule Assembly ◽  
Dependent Manner ◽  
Microtubule Nucleation ◽  
Microtubule Organizing Centers ◽  
Evolutionarily Conserved ◽  
Microtubule Growth ◽  
In Cells

Abstract Microtubules grow not only from the centrosome but also from various noncentrosomal microtubule-organizing centers (MTOCs), including the nuclear envelope (NE) and pre-existing microtubules. The evolutionarily conserved proteins Mto1/CDK5RAP2 and Alp14/TOG/XMAP215 have been shown to be involved in promoting microtubule nucleation. However, it has remained elusive as to how the microtubule nucleation promoting factors are specified to various noncentrosomal MTOCs, particularly the NE, and how these proteins coordinate to organize microtubule assembly. Here, we demonstrate that in the fission yeast Schizosaccharomyces pombe, efficient interphase microtubule growth from the NE requires Alp7/TACC, Alp14/TOG/XMAP215, and Mto1/CDK5RAP2. The absence of Alp7, Alp14, or Mto1 compromises microtubule regrowth on the NE in cells undergoing microtubule repolymerization. We further demonstrate that Alp7 and Mto1 interdependently localize to the NE in cells without microtubules and that Alp14 localizes to the NE in an Alp7 and Mto1-dependent manner. Tethering Mto1 to the NE in cells lacking Alp7 partially restores microtubule number and the efficiency of microtubule generation from the NE. Hence, our study delineates that Alp7, Alp14, and Mto1 work in concert to regulate interphase microtubule regrowth on the NE.

scholarly journals The Ubiquitin Carboxyl Hydrolase BAP1 Forms a Ternary Complex with YY1 and HCF-1 and Is a Critical Regulator of Gene Expression

2010 ◽  
Vol 30 (21) ◽  
pp. 5071-5085 ◽  
Author(s):  
Helen Yu ◽  
Nazar Mashtalir ◽  
Salima Daou ◽  
Ian Hammond-Martel ◽  
Julie Ross ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ternary Complex ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Mitochondrial Protein ◽  
Coiled Coil ◽  
Dependent Manner ◽  
Cellular Processes ◽  
Rich Domain

ABSTRACT The candidate tumor suppressor BAP1 is a deubiquitinating enzyme (DUB) involved in the regulation of cell proliferation, although the molecular mechanisms governing its function remain poorly defined. BAP1 was recently shown to interact with and deubiquitinate the transcriptional regulator host cell factor 1 (HCF-1). Here we show that BAP1 assembles multiprotein complexes containing numerous transcription factors and cofactors, including HCF-1 and the transcription factor Yin Yang 1 (YY1). Through its coiled-coil motif, BAP1 directly interacts with the zinc fingers of YY1. Moreover, HCF-1 interacts with the middle region of YY1 encompassing the glycine-lysine-rich domain and is essential for the formation of a ternary complex with YY1 and BAP1 in vivo. BAP1 activates transcription in an enzymatic-activity-dependent manner and regulates the expression of a variety of genes involved in numerous cellular processes. We further show that BAP1 and HCF-1 are recruited by YY1 to the promoter of the cox7c gene, which encodes a mitochondrial protein used here as a model of BAP1-activated gene expression. Our findings (i) establish a direct link between BAP1 and the transcriptional control of genes regulating cell growth and proliferation and (ii) shed light on a novel mechanism of transcription regulation involving ubiquitin signaling.

Molecular Mechanisms of Antitumor Activity of the Selective Inhibitor of Nuclear Export (SINE) CRM1 Antagonist KPT-185 in Mantle Cell Lymphoma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2438-2438
Author(s):  
Yoko Tabe ◽  
Kensuke Kojima ◽  
Linhua Jin ◽  
Takashi Miida ◽  
Sharon Shacham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Signaling Pathways ◽  
Nuclear Export ◽  
Molecular Mechanisms ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Dependent Manner ◽  
Antitumor Effects

Abstract Abstract 2438 CRM1, a member of the importin b super family of nuclear transport receptors, functions as a major nuclear export factor by shuttling transcription factors including p53, p21, I-kB, and FOXO3a from nucleus to cytoplasm, thereby preventing their activity. CRM1 is also involved in the transport of rRNA and a certain subset of mRNAs including Cyclin D1. Upregulated CRM1 expression has been reported to correlate with poor prognosis in various hematopoietic malignancies. MCL is a subtype of B-cell lymphoma which is frequently resistant to standard chemotherapy. The t(11,14)(q13;32) translocation of MCL juxtaposes the cyclin D1 gene, and constitutively overexpressed cyclin D1 is believed to be associated with oncogenesis. Additional genetic events such as mutation/overexpression of TP53 have been reported as adverse prognostic indicators. TP53 mutations are rare in typical MCL, although about 30% of aggressive blastoid MCL have mt-TP53. Because of the multiple signaling pathways that are dysregulated in MCL, a novel strategy aimed at restoring multiple anti-oncogenetic pathways, especially targeting p53-independent signaling pathways, is of considerable interest. In this study, we investigated the antitumor effects and molecular mechanisms of the SINE CRM1 antagonist KPT-185 (Karyopharm Therapeutics) in 4 MCL cells with known TP53 mutation status (wt-TP53: JVM2, Z138; mt-TP53: MINO, Jeko-1). Treatment with KPT-185 resulted in reduction of cell proliferation in a concentration-dependent manner without significant differences between wt- and mt-TP53 cells (IC50 at 72hrs by trypan blue exclusion method; 35nM for Z138, 92 nM for JVM2, 96 nM for MINO, 103 nM for Jeko-1). KPT-185 exhibited limited pro- apoptotic activity in the tested MCL cells except Z138 (ED50 at 48hrs by Annexin V positivity; 62 nM for Z138, 910 nM for JVM2, 665 nM for MINO, 618 nM for Jeko-1). We then investigated KPT-185-induced TP53 target gene expression changes (24 genes) by TaqMan low density arrays (TLDA) (Applied Biosystems). In wt-TP53 JVM2 and Z138 cells, KPT-185 (100nM for Z138, MINO, and 500nM for JVM2, Jeko-1) upregulated classical p53 targets such as p21 and MDM2 mRNA (>2.0 fold), while there was no increase in mt-TP53 MINO and Jeko-1 cells. Of note, in both wt- and mt-TP53 cells, KPT-185 upregulated gene expression of PUMA which is a target of FOXO3a, p73 and p53 (3.3 fold for JVM2, 2.5 fold for Z138, 3.3 fold for MINO, 4.8 fold for Jeko-1). Recently, CRM1 has been reported to positively modulate the nuclear export of Cyclin D1 mRNA in a eIF4E-dependent manner. We therefore examined Cyclin D1 protein levels by western blot analysis, and observed significantly high baseline expression of Cyclin D1 in Z-138 cells which are highly sensitive to KPT-185, as compared to less sensitive MCL cells. KPT-185 treatment decreased Cyclin D1 expression in a dose-dependent manner (50nM and 100nM) after 12hrs of treatment accompanied by p21 induction and decreased p-Rb. These findings demonstrate that KPT-185 successfully inhibits CRM1 activity in MCL resulting in inhibition of Cyclin D1 and cell proliferation, and in the p-53-independent upregulation of pro-apoptotic PUMA. In conclusion, CRM1 inhibition by KPT-185 results in cell growth inhibition and in moderate cell death in a TP-53 independent manner. Results also suggest that the sensitivity to KPT-185 in MCL may be dependent on Cyclin D1 expression. Therefore, KPT-185may be an effective agent for the treatment of MCL. Disclosures: Shacham: Karyopharm Therapeutics: Employment. Kauffman:Karyopharm Therapeutics Inc: Employment.

scholarly journals Amino acid limitation regulates gene expression

1999 ◽  
Vol 58 (3) ◽  
pp. 625-632 ◽  
Author(s):  
Alain Bruhat ◽  
Céline Jousse ◽  
Pierre Fafournoux
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Essential Amino Acids ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Control Of Gene Expression

In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.

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.

Differential effects of deoxycholic acid and taurodeoxycholic acid on NF-κB signal transduction and IL-8 gene expression in colonic epithelial cells

2004 ◽  
Vol 286 (6) ◽  
pp. G1000-G1008 ◽  
Author(s):  
M. Mühlbauer ◽  
B. Allard ◽  
A. K. Bosserhoff ◽  
S. Kiessling ◽  
H. Herfarth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Deoxycholic Acid ◽  
Nuclear Translocation ◽  
Binding Activity ◽  
Dominant Negative ◽  
Dependent Manner ◽  
Colonic Epithelial Cells

Several effects of bile acids (BAs) on colonic epithelial cells (CECs) have been described, including induction of proliferation and apoptosis. Some of these effects are mediated through activation of the NF-κB transcriptional system. In this study, we investigated the molecular mechanisms underlying the BA-induced gene expression in CECs. The human CEC line HT-29 and primary human CECs were treated with dilutions of salts of deoxycholic acid (DCA) and taurodeoxycholic acid (TDCA). NF-κB binding activity was analyzed with EMSA, RelA translocation with immunofluorescence, and IκBα- and RelA-phosphorylation with Western blot analysis. IL-8 mRNA and protein expression were assessed by quantitative PCR and ELISA. Functional impact of NF-κB activation was determined by blocking the proteasome activity with MG132 or by preventing IKK activity with a dominant-negative IKKβ delivered by adenoviral dominant-negative (dn) IKKβ (Ad5dnIKKβ). DCA and TDCA induced IL-8 expression in a dose- and time-dependent manner. It is interesting that DCA but not TDCA induced IκBα-phophorylation, RelA translocation, and NF-κB binding activity. Accordingly, the proteasome inhibitor MG132 blocked DCA- but not TDCA-induced IL-8 gene expression. In contrast, TDCA-induced IL-8 gene expression correlated with enhanced RelA phosphorylation, which was blocked by Ad5dnIKKβ. Our data suggest that DCA-induced signal transduction mainly utilized the IκB degradation and RelA nuclear translocation pathway, whereas TDCA primarily induced IL-8 gene expression through RelA phosphorylation. These differences may have implications for the understanding of the pathophysiology of inflammation and carcinogenesis in the gut.

scholarly journals Regulation of lipid droplet and membrane biogenesis by the acidic tail of the phosphatidate phosphatase Pah1p

2013 ◽  
Vol 24 (13) ◽  
pp. 2124-2133 ◽  
Author(s):  
Eleftherios Karanasios ◽  
Antonio Daniel Barbosa ◽  
Hiroshi Sembongi ◽  
Muriel Mari ◽  
Gil-Soo Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Important Determinant ◽  
Dependent Manner ◽  
Membrane Biogenesis ◽  
Phosphatidate Phosphatase ◽  
Evolutionarily Conserved ◽  
Important Regulator ◽  
Carboxy Terminal

Lipins are evolutionarily conserved phosphatidate phosphatases that perform key functions in phospholipid, triglyceride, and membrane biogenesis. Translocation of lipins on membranes requires their dephosphorylation by the Nem1p-Spo7p transmembrane phosphatase complex through a poorly understood mechanism. Here we identify the carboxy-terminal acidic tail of the yeast lipin Pah1p as an important regulator of this step. Deletion or mutations of the tail disrupt binding of Pah1p to the Nem1p-Spo7p complex and Pah1p membrane translocation. Overexpression of Nem1p-Spo7p drives the recruitment of Pah1p in the vicinity of lipid droplets in an acidic tail–dependent manner and induces lipid droplet biogenesis. Genetic analysis shows that the acidic tail is essential for the Nem1p-Spo7p–dependent activation of Pah1p but not for the function of Pah1p itself once it is dephosphorylated. Loss of the tail disrupts nuclear structure, INO1 gene expression, and triglyceride synthesis. Similar acidic sequences are present in the carboxy-terminal ends of all yeast lipin orthologues. We propose that acidic tail–dependent binding and dephosphorylation of Pah1p by the Nem1p-Spo7p complex is an important determinant of its function in lipid and membrane biogenesis.

Glucose and forskolin regulate IAPP gene expression through different signal transduction pathways

2001 ◽  
Vol 281 (5) ◽  
pp. E938-E945 ◽  
Author(s):  
Wei-Qun Ding ◽  
Eileen Holicky ◽  
Laurence J. Miller
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Β Cell ◽  
Regulatory Pathways ◽  
Gene Assay ◽  
Kinase A

Molecular mechanisms for the regulation of islet amyloid polypeptide (IAPP) gene expression remain unclear. In the present study, we investigated the effects of glucose and forskolin on IAPP gene regulation in the INS-1 islet β-cell line. Both glucose and forskolin increased the level of expression of this gene, as measured by Northern blot analysis, and increased IAPP gene transcription in a time- and concentration-dependent manner, as demonstrated in a reporter gene assay. Although inhibition of protein kinase A activity with H-89 eliminated the effect of forskolin on this gene, the glucose effect was unaffected. This supported the predominant use of a protein kinase A-independent signaling pathway for glucose regulation of the IAPP gene. Electrophoretic mobility shift assay further indicated that glucose and forskolin regulated expression of this gene by targeting different elements of the promoter. Mutation of the cAMP regulatory element flanking the IAPP coding region resulted in the loss of most of the forskolin-stimulated IAPP gene promoter activity, whereas glucose-enhanced IAPP gene transcription was unaffected. These results demonstrate parallel and distinct regulatory pathways involved in glucose- and forskolin-induced IAPP gene expression in this model β-cell system.

DDX21 interacts with nuclear AGO2 and regulates the alternative splicing of SMN2

2020 ◽  
Vol 85 (2) ◽  
pp. 272-279
Author(s):  
Mengting Gong ◽  
Xi Zhang ◽  
Yaru Wang ◽  
Guiyan Mao ◽  
Yangqi Ou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Gene Silencing ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Dependent Manner ◽  
Indirect Interaction ◽  
Multiple Gene ◽  
Multiple Gene Silencing

ABSTRACT AGO2 is the only member of mammalian Ago protein family that possesses the catalytic activity and plays a central role in gene silencing. Recently researches reported that multiple gene silencing factors, including AGO2, function in the nuclei. The molecular mechanisms of the gene silencing factors functioning in nuclei are conducive to comprehend the roles of gene silencing in pretranslational regulation of gene expression. Here, we report that AGO2 interacts with DDX21 indirectly in an RNA-dependent manner by Co-IP and GST-Pulldown assays and the 2 proteins present nuclei foci in the immunofluorescence experiments. We found that DDX21 up-regulated the protein level of AGO2 and participated in target gene, SNM2, alternative splicing involved in AGO2 by the indirect interaction with AGO2, which produced different transcripts of SMN2 in discrepant expression level. This study laid important experiment foundation for the further analysis of the nuclear functions of gene silencing components.

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