MAPK pathways are conserved and complex mechanisms of signaling in eukaryotic cells. These pathways mediate adaptation to different stress conditions by a core kinase cascade that perceives changes in the environment by different upstream elements and mediates adaptation through transcription factors. In the present work, the transmembrane protein Opy2 has been identified and functionally characterized in Candida albicans. This protein is required to trigger Cek1 phosphorylation by different stimuli such as the resumption of growth from stationary phase or the addition of the cell wall disturbing compounds zymolyase and tunicamycin. opy2 mutants display susceptibility to cell wall disturbing compounds like Congo red. However, it does not play a role in the adaptation to high osmolarity or oxidative stress, in close contrast with the situation for the homologous protein in Saccharomyces cerevisiae. The over-expression of Opy2 in a S. cerevisiae opy2ssk1 mutant partially complemented the osmosensitivity on solid medium by a Hog1-independent mechanism as well as the abnormal morphology observed in this mutant under high osmolarity. The electrophoretic pattern of CaOpy2 tagged version in S. cerevisiae suggested similar post-translational modification in both microorganisms. This protein is also involved in pathogenesis as revealed by the fact that opy2 mutants displayed a significantly reduced virulence in the Galleria mellonella model.
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http://dx.doi.org/10.1016/j.fgb.2012.11.001 | DOI Listing |
Cell Rep
December 2024
Institute of Biochemistry, Christian-Albrechts-University Kiel, Olshausenstrasse 40, 24118 Kiel, Germany. Electronic address:
Genetic variants in TMEM106B, coding for a transmembrane protein of unknown function, have been identified as critical genetic modulators in various neurodegenerative diseases with a strong effect in patients with frontotemporal degeneration. The luminal domain of TMEM106B can form amyloid-like fibrils upon proteolysis. Whether this luminal domain is generated under physiological conditions and which protease(s) are involved in shedding remain unclear.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Center of Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
To successfully apply the genome editing technology using the CRISPR/Cas9 system in the clinic, it is necessary to achieve a high efficiency of knock-in, which is insertion of a genetic construct into a given locus of the target cell genome. One of the approaches to increase the efficiency of knock-in is to modify donor DNA with the same Cas9 targeting sites (CTS) that are used to induce double-strand breaks (DSBs) in the cell genome (the double-cut donor method). Another approach is based on introducing truncated CTS (tCTS), including a PAM site and 16 proximal nucleotides, into the donor DNA.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Center of Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
The low knock-in efficiency, especially in primary human cells, limits the use of the genome editing technology for therapeutic purposes, rendering it important to develop approaches for increasing the knock-in levels. In this work, the efficiencies of several approaches were studied using a model of knock-in of a construct coding for the peptide HIV fusion inhibitor MT-C34 into the human CXCR4 locus in the CEM/R5 T cell line. First, donor DNA modification was evaluated as a means to improve the efficiency of plasmid transport into the nucleus.
View Article and Find Full Text PDFActa Neuropathol Commun
December 2024
Department of Physiology & Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
Mitochondrial dysfunction and α-synuclein (αSyn) aggregation are key contributors to Parkinson's Disease (PD). While genetic and environmental risk factors, including mutations in mitochondrial-associated genes, are implicated in PD, the precise mechanisms linking mitochondrial defects to αSyn pathology remain incompletely understood, hindering the development of effective therapeutic interventions. Here, we identify the loss of branched chain ketoacid dehydrogenase kinase (BCKDK) as a mitochondrial risk factor that exacerbates αSyn pathology by disrupting Complex I function.
View Article and Find Full Text PDFHereditas
December 2024
Facultad de Ciencias Biológicas, Departamento de Biología Celular y Genética, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.
Background: Breast cancer is the most prevalent cancer among women worldwide. Most breast cancer-related deaths result from metastasis and drug resistance. Novel therapies are imperative for targeting metastatic and drug-resistant breast cancer cells.
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