Ceramide signals for initiation of yeast mating-specific cell cycle arrest

Activated Raf has been linked to such opposing cellular responses as the induction of DNA synthesis and the inhibition of proliferation. However, it remains unclear how such a switch in signal specificity is regulated. We have addressed this question with a regulatable Raf-androgen receptor fusion protein in murine fibroblasts. We show that Raf can cause a G1-specific cell cycle arrest through induction of p21Cip1. This in turn leads to inhibition of cyclin D- and cyclin E-dependent kinases and an accumulation of hypophosphorylated Rb. Importantly, this behavior can be observed only in response to a strong Raf signal. In contrast, moderate Raf activity induces DNA synthesis and is sufficient to induce cyclin D expression. Therefore, Raf signal specificity can be determined by modulation of signal strength presumably through the induction of distinct protein expression patterns. Similar to induction of Raf, a strong induction of activated Ras via a tetracycline-dependent promoter also causes inhibition of proliferation and p21Cip1 induction at high expression levels. Thus, p21Cip1 plays a key role in determining cellular responses to Ras and Raf signalling. As predicted by this finding we show that Ras and loss of p21 cooperate to confer a proliferative advantage to mouse embryo fibroblasts.

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Cytolethal distending toxin A, B and C subunit proteins are necessary for the genotoxic effect of Escherichia coli CDT-V

Acta Veterinaria Hungarica ◽

10.1556/avet.2015.001 ◽

2015 ◽

Vol 63 (1) ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Frederic Taieb ◽

Domonkos Sváb ◽

Claude Watrin ◽

Eric Oswald ◽

István Tóth

Keyword(s):

Escherichia Coli ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Pathogenic Bacteria ◽

Genotoxic Effect ◽

Specific Cell ◽

Protein Subunits ◽

Cycle Arrest ◽

Wide Range ◽

C Subunit

Cytolethal distending toxins (CDT) are considered the prototype of inhibitory cyclomodulins, and are produced by a wide range of Gram-negative pathogenic bacteria, includingEscherichia colistrains of various sero- and pathotypes. CDT is a heterotripartite toxin consisting of three protein subunits, CdtA, CdtB and CdtC. The active subunit, CdtB has DNase activity and causes DNA damage and cell cycle arrest in the target cell. However, several studies have highlighted different roles for CdtA and CdtC subunits. In order to reveal the necessity of CdtA and CdtC subunit proteins in the CDT-specific phenotype, expression clones containing thecdt-Vsubunit genes were constructed. Using cell culture assays, we demonstrated that clones expressing only the CdtB subunit or in combination with only CdtA or CdtC were unable to trigger the specific cell cycle arrest and changes in cell morphology in HeLa cells. At the same time, the recombinant clone harbouring the wholecdt-Voperon caused all the CDT-associated characteristic phenotypes. All these results verify that all the three CDT subunit proteins are necessary for the genotoxic effect caused by CDT-V.

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Mating-type-specific cell cycle arrest and shmoo formation by ? pheromone of Saccharomyces cerevisiae in Hansenula wingei

Archives of Microbiology ◽

10.1007/bf00415615 ◽

1983 ◽

Vol 136 (1) ◽

pp. 79-80 ◽

Cited By ~ 6

Author(s):

Hiroaki Fujimura ◽

Naohiko Yanagishima

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Mating Type ◽

Specific Cell ◽

Cycle Arrest ◽

Hansenula Wingei

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Campylobacter jejuni Cytolethal Distending Toxin Causes a G2-Phase Cell Cycle Block

Infection and Immunity ◽

10.1128/iai.66.5.1934-1940.1998 ◽

1998 ◽

Vol 66 (5) ◽

pp. 1934-1940 ◽

Cited By ~ 166

Author(s):

Chris A. Whitehouse ◽

Paul B. Balbo ◽

Everett C. Pesci ◽

Daniel L. Cottle ◽

Peter M. Mirabito ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Campylobacter Jejuni ◽

Hela Cells ◽

Chromatin Condensation ◽

Phase Cell ◽

Specific Cell ◽

Cytolethal Distending Toxin ◽

Cycle Arrest ◽

M Phase

ABSTRACT Cytolethal distending toxin (CDT) from the diarrheagenic bacteriumCampylobacter jejuni was shown to cause a rapid and specific cell cycle arrest in HeLa and Caco-2 cells. Within 24 h of treatment, CDT caused HeLa cells to arrest with a 4N DNA content, indicative of cells in G2 or early M phase. Immunofluorescence studies indicated that the arrested cells had not entered M phase, since no evidence of tubulin reorganization or chromatin condensation was visible. CDT treatment was also shown to cause HeLa cells to accumulate the inactive, tyrosine-phosphorylated form of CDC2. These results indicated that CDT treatment results in a failure to activate CDC2, which leads to cell cycle arrest in G2. This mechanism of action is novel for a bacterial toxin and provides a model for the generation of diarrheal disease byC. jejuni and other diarrheagenic bacteria that produce CDT.

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Cytotoxic Effect of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) on Liver Cancer Cell Integrated with Hepatitis B Genome, Hep3B

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/1549805 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 4

Author(s):

Aminah Suhaila Haron ◽

Sharifah Sakinah Syed Alwi ◽

Latifah Saiful Yazan ◽

Rohaina Abd Razak ◽

Yong Sze Ong ◽

...

Keyword(s):

Cell Cycle ◽

Liver Cancer ◽

Hepatitis B ◽

Cell Cycle Arrest ◽

Nigella Sativa ◽

Drug Carrier ◽

Specific Cell ◽

Nanostructured Lipid Carrier ◽

B Genome ◽

Cycle Arrest

Thymoquinone (TQ), a bioactive compound found in Nigella sativa, cannot be orally consumed due to its lipophilicity. In order to overcome this low bioavailability, TQ is loaded into a colloidal drug carrier known as a nanostructured lipid carrier (NLC). This study aims to determine the antiproliferative effects of TQ and TQ-NLC on liver cancer cells integrated with the hepatitis B genome, Hep3B. The Hep3B was treated with TQ or TQ-NLC for 24, 48, and 72 hours via MTT assay. The results confirm that TQ or TQ-NLC inhibited the growth of Hep3B at IC50 <16.7 μM for 72 hours. TQ was also found to induce cell cycle arrest at the G1 checkpoint while TQ-NLC induced non-phase-specific cell cycle arrest. Further analysis using Annexin V staining confirmed the apoptotic induction of TQ or TQ-NLC via activation of caspases-3/7. In ROS management, TQ acted as a prooxidant (increased the level of ROS), while TQ-NLC acted as an antioxidant (reduced the level of ROS). Molecular analysis demonstrated that the GSH system and the Nrf2/Keap1 signaling pathway in Hep3B influenced the differential responses of the cells towards TQ or TQ-NLC. Hence, this study demonstrated that TQ and TQ-NLC have in vitro anticancer effects on the Hep3B.

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