scholarly journals Menin Is a Regulator of the Stress Response in Drosophila melanogaster

2005 ◽  
Vol 25 (22) ◽  
pp. 9960-9972 ◽  
Author(s):  
Maria Papaconstantinou ◽  
Ying Wu ◽  
Hendrik Nikolaas Pretorius ◽  
Nishi Singh ◽  
Gabriella Gianfelice ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Rna Interference ◽  
Stress Response ◽  
Heat Shock ◽  
Model Organism ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Control Of Gene Expression ◽  
Damage Sensing ◽  
Mitogen Activated Protein

ABSTRACT Menin, the product of the multiple endocrine neoplasia type I gene, has been implicated in several biological processes, including the control of gene expression and apoptosis, the modulation of mitogen-activated protein kinase pathways, and DNA damage sensing or repair. In this study, we have investigated the function of menin in the model organism Drosophila melanogaster. We show that Drosophila lines overexpressing menin or an RNA interference for this gene develop normally but are impaired in their response to several stresses, including heat shock, hypoxia, hyperosmolarity and oxidative stress. In the embryo subjected to heat shock, this impairment was characterized by a high degree of developmental arrest and lethality. The overexpression of menin enhanced the expression of HSP70 in embryos and interfered with its down-regulation during recovery at the normal temperature. In contrast, the inhibition of menin with RNA interference reduced the induction of HSP70 and blocked the activation of HSP23 upon heat shock, Menin was recruited to the Hsp70 promoter upon heat shock and menin overexpression stimulated the activity of this promoter in embryos. A 70-kDa inducible form of menin was expressed in response to heat shock, indicating that menin is also regulated in conditions of stress. The induction of HSP70 and HSP23 was markedly reduced or absent in mutant embryos harboring a deletion of the menin gene. These embryos, which did not express the heat shock-inducible form of menin, were also hypersensitive to various conditions of stress. These results suggest a novel role for menin in the control of the stress response and in processes associated with the maintenance of protein integrity.

scholarly journals Rox3 and Rts1 Function in the Global Stress Response Pathway in Baker's Yeast

Genetics ◽  
1996 ◽  
Vol 142 (4) ◽  
pp. 1083-1093 ◽  
Author(s):  
Carlos C Evangelista ◽  
Ana M Rodriguez Torres ◽  
M Paullin Limbach ◽  
Richard S Zitomer
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Osmotic Stress ◽  
Regulatory Element ◽  
Regulatory Region ◽  
Mitogen Activated Protein Kinase ◽  
Regulatory Subunit ◽  
Temperature Sensitive ◽  
Global Stress ◽  
Rna Accumulation

Abstract Yeast respond to a variety of stresses through a global stress response that is mediated by a number of signal transduction pathways and the cis-acting STRE DNA sequence. The CYC7 gene, encoding iso-2-cytochrome c, has been demonstrated to respond to heat shock, glucose starvation, approach-to-stationary phase, and, as we demonstrate here, to osmotic stress. This response was delayed in a the hogl-Δ1 strain implicating the Hog1 mitogen-activated protein kinase cascade, a known component of the global stress response. Deletion analysis of the CYC7 regulatory region suggested that three STRE elements were each capable of inducing the stress response. Mutations in the ROX3 gene prevented CYC7 RNA accumulation during heat shock and osmotic stress. ROX3 RNA levels were shown to be induced by stress through a novel regulatory element. A selection for high-copy suppressors of a ROX3 temperature-sensitive allele resulted in the isolation of RTS1, encoding a protein with homology to the B′ regulatory subunit of protein phosphatase 2A0. Deletion of RTS1 caused temperature and osmotic sensitivity and increased accumulation of CYC7 RNA under all conditions. Over-expression of this gene caused increased CYC7 RNA accumulation in rox3 mutants but not in wild-type cells.

scholarly journals Specific Activation of Mitogen-activated Protein Kinase by Transforming Growth Factor-β Receptors in Lipid Rafts Is Required for Epithelial Cell Plasticity

2009 ◽  
Vol 20 (3) ◽  
pp. 1020-1029 ◽  
Author(s):  
Wei Zuo ◽  
Ye-Guang Chen
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Protein Kinase ◽  
Lipid Rafts ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Coated Pits ◽  
Mapk Activation ◽  
Mitogen Activated Protein

Transforming growth factor (TGF)-β regulates a spectrum of cellular events, including cell proliferation, differentiation, and migration. In addition to the canonical Smad pathway, TGF-β can also activate mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and small GTPases in a cell-specific manner. Here, we report that cholesterol depletion interfered with TGF-β–induced epithelial-mesenchymal transition (EMT) and cell migration. This interference is due to impaired activation of MAPK mediated by cholesterol-rich lipid rafts. Cholesterol-depleting agents specifically inhibited TGF-β–induced activation of extracellular signal-regulated kinase (ERK) and p38, but not Smad2/3 or Akt. Activation of ERK or p38 is required for both TGF-β–induced EMT and cell migration, whereas PI3K/Akt is necessary only for TGF-β–promoted cell migration but not for EMT. Although receptor heterocomplexes could be formed in both lipid raft and nonraft membrane compartments in response to TGF-β, receptor localization in lipid rafts, but not in clathrin-coated pits, is important for TGF-β–induced MAPK activation. Requirement of lipid rafts for MAPK activation was further confirmed by specific targeting of the intracellular domain of TGF-β type I receptor to different membrane locations. Together, our findings establish a novel link between cholesterol and EMT and cell migration, that is, cholesterol-rich lipid rafts are required for TGF-β–mediated MAPK activation, an event necessary for TGF-β–directed epithelial plasticity.

scholarly journals Activation of mitogen-activated protein kinase kinase (MKK) 3 and MKK6 by type I interferons. VOLUME 280 (2005) 10001-10010

2006 ◽  
Vol 281 (15) ◽  
pp. 10651
Author(s):  
Yongzhong Li ◽  
Sandeep Batra ◽  
Antonella Sassano ◽  
Beata Majchrzak ◽  
David E. Levy ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Type I Interferons ◽  
Type I ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

scholarly journals Vaccinia-Related Kinase 2 Modulates the Stress Response to Hypoxia Mediated by TAK1

2007 ◽  
Vol 27 (20) ◽  
pp. 7273-7283 ◽  
Author(s):  
Sandra Blanco ◽  
Claudio Santos ◽  
Pedro A. Lazo
Keyword(s):  
Stress Response ◽  
Cellular Response ◽  
Mapk Signaling ◽  
Cellular Stress Response ◽  
Mitogen Activated Protein Kinase ◽  
Stable Complex ◽  
Intracellular Proteins ◽  
Mitogen Activated Protein ◽  
Jnk Activation ◽  
Protein Kinase Kinase

ABSTRACT Hypoxia represents a major stress that requires an immediate cellular response in which different signaling pathways participate. Hypoxia induces an increase in the activity of TAK1, an atypical mitogen-activated protein kinase kinase kinase (MAPKKK), which responds to oxidative stress by triggering cascades leading to the activation of c-Jun N-terminal kinase (JNK). JNK activation by hypoxia requires assembly with the JIP1 scaffold protein, which might also interact with other intracellular proteins that are less well known but that might modulate MAPK signaling. We report that TAK1 is able to form a stable complex with JIP1 and thus regulate the activation of JNK, which in turn determines the cellular stress response to hypoxia. This activation of TAK1-JIP1-JNK is suppressed by vaccinia-related kinase 2 (VRK2). VRK2A is able to interact with TAK1 by its C-terminal region, forming stable complexes. The kinase activity of VRK2 is not necessary for this interaction or the downregulation of AP1-dependent transcription. Furthermore, reduction of the endogenous VRK2 level with short hairpin RNA can increase the response induced by hypoxia, suggesting that the intracellular levels of VRK2 can determine the magnitude of this stress response.

scholarly journals The Mitogen-Activated Protein Kinase Slt2 Regulates Nuclear Retention of Non-Heat Shock mRNAs during Heat Shock-Induced Stress

2010 ◽  
Vol 30 (21) ◽  
pp. 5168-5179 ◽  
Author(s):  
Sean R. Carmody ◽  
Elizabeth J. Tran ◽  
Luciano H. Apponi ◽  
Anita H. Corbett ◽  
Susan R. Wente
Keyword(s):  
Heat Shock ◽  
Map Kinase ◽  
Mrna Export ◽  
Mitogen Activated Protein Kinase ◽  
Focus Formation ◽  
Mrna Accumulation ◽  
Heat Shock Stress ◽  
Mitogen Activated Protein ◽  
Nuclear Foci ◽  
Shock Stress

ABSTRACT Cellular adaptation to environmental stress conditions requires rapid and specific changes in gene expression. During heat shock, most polyadenylated mRNAs are retained in the nucleus, whereas the export of heat shock-induced mRNAs is allowed. Although essential mRNA export factors are known, the precise mechanism for regulating transport is not fully understood. Here we find that during heat shock in Saccharomyces cerevisiae, the mRNA-binding protein Nab2 is phosphorylated on threonine 178 and serine 180 by the mitogen-activated protein (MAP) kinase Slt2/Mpk1. Slt2 is required for nuclear poly(A+) mRNA accumulation upon heat shock, and thermotolerance is decreased in a nup42 nab2-T178A/S180A mutant. Coincident with phosphorylation, Nab2 and Yra1 colocalize in nuclear foci with Mlp1, a protein involved in mRNA retention. Nab2 nuclear focus formation and Nab2 phosphorylation are independent, suggesting that heat shock induces multiple cellular alterations that impinge upon transport efficiency. Under normal conditions, we find that the mRNA export receptor Mex67 and Nab2 directly interact. However, upon heat shock stress, Mex67 does not localize to the Mlp1 nuclear foci, and its association with Nab2 complexes is reduced. These results reveal a novel mechanism by which the MAP kinase Slt2 and Mlp1 control mRNA export factors during heat shock stress.

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