Eukaryotic cell cycle progression in response to environmental conditions is controlled via specific checkpoints. Signal transduction pathways mediated by MAPKs play a crucial role in sensing stress. For example, the canonical MAPKs Mkc1 (of the cell wall integrity pathway), and Hog1 (of the HOG pathway), are activated upon oxidative stress. In this work, we have analyzed the effect of oxidative stress induced by hydrogen peroxide on cell cycle progression in . Hydrogen peroxide was shown to induce a transient arrest at the G1 phase of the cell cycle. Specifically, a G1 arrest was observed, although phosphorylation of Mkc1 and Hog1 MAPKs can take place at all stages of the cell cycle. Interestingly, (but not ) mutants required a longer time compared to wild type cells to resume growth after hydrogen peroxide challenge. Using GFP-labeled cells and mixed cultures of wild type and cells we were able to show that mutants progress faster through the cell cycle under standard growth conditions in the absence of stress (YPD at 37°C). Consequently, mutants exhibited a smaller cell size. The altered cell cycle progression correlates with altered expression of the G1 cyclins Cln3 and Pcl2 in cells compared to the wild type strain. In addition, Hgc1 (a hypha-specific G1 cyclin) as well as Cln3 displayed a different kinetics of expression in the presence of hydrogen peroxide in mutants. Collectively, these results indicate that Hog1 regulates the expression of G1 cyclins not only in response to oxidative stress, but also under standard growth conditions. Hydrogen peroxide treated cells did not show fluctuations in the mRNA levels for , which are observed in untreated cells during cell cycle progression. In addition, treatment with hydrogen peroxide prevented degradation of Sol1, an effect which was enhanced in mutants. Therefore, in , the MAPK Hog1 mediates cell cycle progression in response to oxidative stress, and further participates in the cell size checkpoint during vegetative growth.
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http://dx.doi.org/10.3389/fmicb.2016.02133 | DOI Listing |
Mol Biol (Mosk)
December 2024
Institute of Functional Genomics, Moscow State University, Moscow, 119991 Russia.
The CRISPR/Cas technology of targeted genome editing made it possible to carry out genetic engineering manipulations with eukaryotic genomes with a high efficiency. Targeted induction of site-specific DNA breaks is one of the key stages of the technology. The cell repairs the breaks via one of the two pathways, nonhomologous end joining (NHEJ) and homology-driven repair (HDR).
View Article and Find Full Text PDFJ Biol Eng
December 2024
Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA.
Glioblastoma tumors are the most common and aggressive adult central nervous system malignancy. Nearly all patients experience disease progression, which significantly contributes to disease mortality. Recently, it has been suggested that recurrent tumors may be characterized by a ferroptosis-prone phenotype with a significant decrease in glutathione peroxidase 4 (GPx4) expression.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
December 2024
Department of Oncology, Molecular Biotechnology Center "G. Tarone", University of Torino, Piazza Nizza 44, Torino, 10126, Italy.
Background: Malignant pleural mesothelioma (MPM) is a highly chemo-refractory and immune-evasive tumor that presents a median overall survival of 12-14 months when treated with chemotherapy and immunotherapy. New anti-tumor therapies as well as the concomitant reactivation of immune destruction are urgently needed to treat patients with this tumor. The aim of this work is to investigate the potential effect of ecteinascidin derivatives as lurbinectedin as new first-line treatment option in MPM, alone and in combination with immunotherapy.
View Article and Find Full Text PDFBMC Womens Health
December 2024
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China.
Background: The aim of this study was to compare the effectiveness of two different vitrification methods and slow freezing in terms of the recovery of endocrine function, follicular morphology and proliferation, apoptosis of stromal cells, and angiogenesis after heterotopic transplantation of human ovarian tissue.
Methods: Ovarian tissue from young women aged 29 to 40 was subjected to two vitrification methods and one slow freezing method. The thawed ovarian tissue was then transplanted into nude mice and divided into three groups (VF1 group, VF2 group, SF group) according to the different freezing methods.
Steroids
December 2024
Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address:
Toad venom, a family of toxic yet pharmacologically valuable biotoxins, has long been utilized in traditional medicine and holds significant promise in modern drug development. Bufotalin, a prominent bufotoxin, has demonstrated potent cytotoxic properties through mechanisms such as apoptosis induction, cell cycle arrest, endoplasmic reticulum stress activation, and inhibition of metastasis by modulating key pathways including Akt, p53, and STAT3/EMT signaling-these multi-target mechanisms position bufotalin as a promising agent to combat multidrug resistance in cancer therapy. Additionally, advances in bufotalin synthesis, including chemical and biocatalytic methods, have streamlined production, with strategies such as C14-α-hydroxylation and novel coupling techniques enhancing yield and reducing environmental impact.
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