scholarly journals Transfer–messenger RNA controls the translation of cell‐cycle and stress proteins in Streptomyces

EMBO Reports ◽  
2009 ◽  
Vol 11 (2) ◽  
pp. 119-125 ◽  
Author(s):  
Sharief Barends ◽  
Martin Zehl ◽  
Sylwia Bialek ◽  
Ellen de Waal ◽  
Bjørn A Traag ◽  
...  
2009 ◽  
Vol 2 ◽  
pp. CGM.S2596 ◽  
Author(s):  
Shona T. Dougherty ◽  
Sean E. Walker ◽  
Peter D. Davis ◽  
Graeme J. Dougherty

The efficacy of approaches in which vascular disrupting agents (VDA) are used in combination with conventional chemotherapy and/or radiation therapy in the treatment of cancer might be improved if there were a better understanding of the cellular and molecular changes induced in normal and malignant cells as a result of VD A exposure. Toward this goal, murine endothelial cells were treated in vitro with ANG501, a novel stilbene VDA developed in our laboratory, and alterations in gene expression determined by genome-wide microarray analysis and subsequently confirmed by Western blot analysis. Among the genes that were shown to be induced upon brief exposure to non-cytotoxic doses of ANG501 were several involved in the control of cell cycle progression and apoptosis, including p21Wafl and the heat shock/stress proteins hsp25, hsp70 and anti-B-crystallin. Reflecting such induction, functional studies confirmed that normal cell cycling is temporarily inhibited following treatment with ANG501 such that the majority of cells accumulate at the radiation-sensitive G2/M phase of the cell cycle at 6 hr. The effects were transient and by 24 hr normal cell cycling had largely resumed. Combination experiments confirmed that endothelial cells treated 6 hr previously with ANG501 were more readily killed by radiation. Importantly, significant effects were evident at clinically relevant radiation doses. Taken together these findings emphasize the need to consider the radiosensitizing activity of VD As when developing therapies in which these promising compounds are used in combination with radiation.


1979 ◽  
Vol 81 (1) ◽  
pp. 123-136 ◽  
Author(s):  
N Agabian ◽  
M Evinger ◽  
G Parker

An essential event in developmental processes is the introduction of asymmetry into an otherwise undifferentiated cell population. Cell division in Caulobacter is asymmetric; the progeny cells are structurally different and follow different sequences of development, thus providing a useful model system for the study of differentiation. Because the progeny cells are different from one another, there must be a segregation of morphogenetic and informational components at some time in the cell cycle. We have examined the pattern of specific protein segregation between Caulobacter stalked and swarmer daughter cells, with the rationale that such a progeny analysis would identify both structurally and developmentally important proteins. To complement the study, we have also examined the pattern of protein synthesis during synchronous growth and in various cellular fractions. We show here, for the first time, that the association of proteins with a specific cell type may result not only from their periodicity of synthesis, but also from their pattern of distribution at the time of cell division. Several membrane-associated and soluble proteins are segregated asymmetrically between progeny stalked and swarmer cells. The data further show that a subclass of soluble proteins becomes associated with the membrane of the progeny stalked cells. Therefore, although the principal differentiated cell types possess different synthetic capabilities and characteristic proteins, the asymmetry between progeny stalked and swarmer cells is generated primarily by the preferential association of specific soluble proteins with the membrane of only one daughter cell. The majority of the proteins which exhibit this segregation behavior are synthesized during the entire cell cycle and exhibit relatively long, functional messenger RNA half-lives.


2003 ◽  
Vol 23 (4) ◽  
pp. 449-461 ◽  
Author(s):  
Wulf Paschen ◽  
Christoph Aufenberg ◽  
Svenja Hotop ◽  
Thorsten Mengesdorf

Cells respond to conditions associated with endoplasmic reticulum (ER) dysfunction with activation of the unfolded protein response, characterized by a shutdown of translation and induction of the expression of genes coding for ER stress proteins. The genetic response is based on IRE1-induced processing of xbp1 messenger RNA (mRNA), resulting in synthesis of new XBP1proc protein that functions as a potent transcription factor for ER stress genes. xbp1 processing in models of transient global and focal cerebral ischemia was studied. A marked increase in processed xbp1 mRNA levels during reperfusion was observed, most pronounced (about 35-fold) after 1-h occlusion of the right middle cerebral artery. The rise in processed xbp1 mRNA was not paralleled by a similar increase in XBP1proc protein levels because transient ischemia induces severe suppression of translation. As a result, mRNA levels of genes coding for ER stress proteins were only slightly increased, whereas mRNA levels of heat-shock protein 70 rose about 550-fold. Under conditions associated with ER dysfunction, cells require activation of the entire ER stress-induced signal transduction pathway, to cope with this severe form of stress. After transient cerebral ischemia, however, the block of translation may prevent synthesis of new XBP1proc protein and thus hinder recovery from ischemia-induced ER dysfunction.


2017 ◽  
Vol 65 (7) ◽  
pp. 1084-1088 ◽  
Author(s):  
Xiao-Jing Yu ◽  
Tie-Jun Song ◽  
Lu-Wei Zhang ◽  
Ying Su ◽  
Ke-Yu Wang ◽  
...  

Psoriasis is a chronic skin disease characterized by abnormal keratinocyte proliferation and differentiation, inflammation, and angiogenesis. Overexpression of tribbles homolog3 (TRB3), which belongs to the tribbles family of pseudokinases, has been found in several human tumors and metabolic diseases, but its role in psoriasis has not been fully clarified. The aim of this study is to investigate the expression of TRB3 in psoriasis and explore its roles in the proliferation of keratinocytes. Twenty-four patients with psoriasis vulgaris were recruited for the study. Diagnosis of psoriasis was based on clinical and histologic examinations. Immunohistochemistry and real-time reverse transcription PCR (RT-PCR) were performed to determine protein and messenger RNA (mRNA) expression of TRB3 in psoriasis lesions. 5-Bromo-2-deoxyUridine (BrdU) incorporation assay were performed for cell proliferation. Cell cycle distribution was assessed by flow cytometry analysis. The levels of TRB3 is elevated in psoriatic lesions compared with psoriatic non-lesions. The HaCat cells expressed the TRB3 gene. We found TRB3 silencing to significantly inhibit HaCat cell proliferation. Furthermore, the specific knockdown of TRB3 slowed down the cell cycle at the gap 0/first gap phase. In conclusion, our data suggest that TRB3 is overexpressed in lesions of patients with psoriasis and may be involved in the abnormal proliferation of keratinocytes. Therefore, TRB3 may be a potential therapeutic target for psoriasis.


2006 ◽  
Vol 175 (3) ◽  
pp. 415-426 ◽  
Author(s):  
Biljana Culjkovic ◽  
Ivan Topisirovic ◽  
Lucy Skrabanek ◽  
Melisa Ruiz-Gutierrez ◽  
Katherine L.B. Borden

This study demonstrates that the eukaryotic translation initiation factor eIF4E is a critical node in an RNA regulon that impacts nearly every stage of cell cycle progression. Specifically, eIF4E coordinately promotes the messenger RNA (mRNA) export of several genes involved in the cell cycle. A common feature of these mRNAs is a structurally conserved, ∼50-nucleotide element in the 3′ untranslated region denoted as an eIF4E sensitivity element. This element is sufficient for localization of capped mRNAs to eIF4E nuclear bodies, formation of eIF4E-specific ribonucleoproteins in the nucleus, and eIF4E-dependent mRNA export. The roles of eIF4E in translation and mRNA export are distinct, as they rely on different mRNA elements. Furthermore, eIF4E-dependent mRNA export is independent of ongoing RNA or protein synthesis. Unlike the NXF1-mediated export of bulk mRNAs, eIF4E-dependent mRNA export is CRM1 dependent. Finally, the growth-suppressive promyelocytic leukemia protein (PML) inhibits this RNA regulon. These data provide novel perspectives into the proliferative and oncogenic properties of eIF4E.


Science ◽  
1975 ◽  
Vol 189 (4202) ◽  
pp. 557-558 ◽  
Author(s):  
J. Stein ◽  
C. Thrall ◽  
W. Park ◽  
R. Mans ◽  
G. Stein

1999 ◽  
Vol 46 (1) ◽  
pp. 197-202 ◽  
Author(s):  
J Fronk

Messenger RNA levels of three ras-family genes (Ppras1, Ppras2, and Pprap1) were measured in different life forms and throughout the cell cycle of the slime mold Physarum polycephalum. All three genes are expressed at constant rates in the uninucleate amoebae and flagellates, regardless of the culture conditions (solid or liquid medium, particulate or dissolved nutrients). In the multinucleate stages (micro- and macroplasmodia) Ppras1 and Pprap1 mRNAs are somewhat less abundant, while Ppras2 is not expressed at all. The early stages of the amoeba-plasmodium transition proceed without any drop in Ppras2 expression. During the synchronous cell cycle in macroplasmodia Ppras1 and Pprap1 are expressed at a constant level.


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