Expression of the yeast glycogen phosphorylase gene is regulated by stress-response elements and by the HOG MAP kinase pathway

Yeast ◽  
2001 ◽  
Vol 18 (16) ◽  
pp. 1505-1514 ◽  
Author(s):  
Susan Wohler Sunnarborg ◽  
Stephen P. Miller ◽  
Indira Unnikrishnan ◽  
David C. LaPorte
Keyword(s):  
Stress Response ◽  
Map Kinase ◽  
Glycogen Phosphorylase ◽  
Response Elements ◽  
Map Kinase Pathway ◽  
Yeast Glycogen ◽  
Kinase Pathway

The Role of DNA Damage/Stress Response Pathways in the Mechanism of Action of Decitabine

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 490-490 ◽  
Author(s):  
Vinzon Ibanez ◽  
Virryan Banzon ◽  
Tatiana Kousnetzova ◽  
Kestis Vaitkus ◽  
Kenneth Peterson ◽  
...  
Keyword(s):  
Dna Damage ◽  
Stress Response ◽  
Map Kinase ◽  
Cell Line ◽  
Erythroid Differentiation ◽  
P38 Map Kinase ◽  
Erythroid Progenitors ◽  
Map Kinase Pathway ◽  
Terminal Erythroid Differentiation ◽  
Kinase Pathway

Abstract The DNA methyltransferase (DNMT) inhibitor decitabine increases fetal hemoglobin (HbF) in experimental primates and to therapeutic levels in patients with sickle cell disease. Decitabine-DNMT covalent adducts formed following incorporation of decitabine into newly synthesized DNA can activate DNA damage/stress response signal transduction pathways. To test the hypothesis that DNA damage/stress response pathways are involved in the ability of decitabine to increase γ-globin expression, experiments were performed in a chemical inducer of dimerization (CID)-dependent mouse fetal bone marrow (BM)-derived cell line containing the human β-globin gene locus in the context of a yeast artificial chromosome and in primary baboon erythroid progenitors derived from CD34+ BM cells grown in Iscove’s media containing 30% fetal bovine serum, 2U/ml epo, 200ng/ml SCF, and 1uM dexamethasone. Addition of decitabine (1μM) to both the CID-dependent mouse BM cell line and erythroid progenitors on day 7 of culture increased phospho-H2A.X and phospho-p38 in Western blot assays demonstrating activation of the ATM/ATR and p38 MAP kinase signal transduction pathways. Decitabine increased γ-globin 280 fold and ε-globin 38 fold in the mouse BM cell line as determined by real time PCR using the ΔΔCT method with mouse α-globin as the standard. Co-addition of the p38 MAP kinase inhibitor SB203580 reduced γ-globin induction 93.4% and ε-globin induction 88.4% in the mouse BM cell line. In primary erythroid progenitors, decitabine increased γ-globin 2.8 fold and ε-globin 44 fold. SB203580 reduced decitabine-mediated ε-globin induction 46% while no significant effect on the level of γ-globin induction was observed. Decitabine also increased phospho-CREB in the mouse BM cell line, a target of the p38 MAP kinase pathway required for γ-globin induction by histone deacetylase inhibitors. These results suggest that activation of the p38 MAP kinase pathway is required for induction of ε- and γ-globin expression by decitabine in the mouse fetal BM cell line and may contribute to increased ε-globin expression in primary erythroid progenitors. Additional Western blot analysis showed that decitabine treatment of erythroid progenitors increased p21WAF1 and p27KIP1 48–72 hours following addition of drug. Examination of Wright’s stained cytospin preparations from decitabine-treated cultured erythroid progenitors showed that orthochromatic erythroblasts were increased >2 fold and basophilic erythroblasts were decreased 5 fold compared to untreated controls 96–120 hours post-drug addition at doses ranging from 0.125 to 1.0mM. These results demonstrate that decitabine increases terminal erythroid differentiation within this cell population. As RB protein is required for cell cycle exit and terminal erythroid differentiation, we suggest that induction of terminal differentiation by decitabine is mediated by the effect of increased p21WAF1 and p27KIP1 on RB phosphorylation. Because of the known asynchrony of γ- and β-globin expression during erythroid differentiation, the ability of decitabine to induce terminal erythroid differentiation could play a role in its ability to increase γ-globin expression. We conclude that activation of DNA damage/stress response pathways by decitabine may contribute to its ability to increase γ-globin expression and induce terminal erythroid differentiation.

577: The RAF/MAP Kinase Pathway Influences Survival in Androgen-Insensitive Prostate Cancer

2005 ◽  
Vol 173 (4S) ◽  
pp. 157-158
Author(s):  
Rono Mukherjee ◽  
Sarath K. Nalagatla ◽  
Mark A. Undenvood ◽  
John M.S. Bartlett ◽  
Joanne Edwards
Keyword(s):  
Prostate Cancer ◽  
Map Kinase ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals Development of anticancer drugs targeting the MAP kinase pathway

Oncogene ◽  
2000 ◽  
Vol 19 (56) ◽  
pp. 6594-6599 ◽  
Author(s):  
Judith S Sebolt-Leopold
Keyword(s):  
Map Kinase ◽  
Anticancer Drugs ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals The MADD-3 LAMMER Kinase Interacts with a p38 MAP Kinase Pathway to Regulate the Display of the EVA-1 Guidance Receptor in Caenorhabditis elegans

PLoS Genetics ◽  
2016 ◽  
Vol 12 (4) ◽  
pp. e1006010 ◽  
Author(s):  
Serena A. D’Souza ◽  
Luckshi Rajendran ◽  
Rachel Bagg ◽  
Louis Barbier ◽  
Derek M. van Pel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Caenorhabditis Elegans ◽  
Map Kinase ◽  
Motor Neurons ◽  
Leading Edge ◽  
P38 Map Kinase ◽  
Endosomal Trafficking ◽  
Guidance Cue ◽  
Map Kinase Pathway ◽  
Kinase Pathway

The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues. We previously discovered that MADD-4, which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans, interacts with an UNC-40/EVA-1 co-receptor complex on muscles to attract plasma membrane extensions called muscle arms. In nematodes, the muscle arm termini harbor the post-synaptic elements of the neuromuscular junction. Through a forward genetic screen for mutants with disrupted muscle arm extension, we discovered that a LAMMER kinase, which we call MADD-3, is required for the proper display of the EVA-1 receptor on the muscle’s plasma membrane. Without MADD-3, EVA-1 levels decrease concomitantly with a reduction of the late-endosomal marker RAB-7. Through a genetic suppressor screen, we found that the levels of EVA-1 and RAB-7 can be restored in madd-3 mutants by eliminating the function of a p38 MAP kinase pathway. We also found that EVA-1 and RAB-7 will accumulate in madd-3 mutants upon disrupting CUP-5, which is a mucolipin ortholog required for proper lysosome function. Together, our data suggests that the MADD-3 LAMMER kinase antagonizes the p38-mediated endosomal trafficking of EVA-1 to the lysosome. In this way, MADD-3 ensures that sufficient levels of EVA-1 are present to guide muscle arm extension towards the source of the MADD-4 guidance cue.

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