Fertilization is the fundamental process in which two gametes - sperm and oocyte - fuse to generate a zygote that will form a new multicellular organism. In most vertebrates, oocytes await fertilization while arrested at metaphase of meiosis II. This resting state can be stable for many hours and depends on a cytoplasmic activity termed cytostatic factor (CSF). Recently, members of the novel Emi/Erp family of proteins have been put forward as important components of CSF. These proteins inhibit the anaphase-promoting complex/cyclosome (APC/C), which acts at the very core of the cell cycle regulatory machinery. Initially, Xenopus early mitotic inhibitor 1 (Emi1) was proposed to be a component of CSF, but newer work suggests that a structural relative, Emi-related protein 1 (Erp1/Emi2), is essential for maintenance of CSF arrest in Xenopus. Most importantly, studies on Erp1/Emi2 regulation have led to a detailed molecular understanding of the Ca2+-mediated release from CSF arrest that occurs upon fertilization.
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http://dx.doi.org/10.1242/jcs.02919 | DOI Listing |
Front Cell Dev Biol
December 2024
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Changes to the composition of the microbiome in neoplasia, is termed oncobiosis, may affect tumor behavior through the changes to the secretion of bacterial metabolites. In this study we show, that ursodeoxycholic acid (UDCA), a bacterial metabolite, has cytostatic properties in pancreatic adenocarcinoma cell (PDAC) models. UDCA in concentrations corresponding to the human serum reference range suppressed PDAC cell proliferation.
View Article and Find Full Text PDFOncol Lett
February 2025
American Foundation for Chinese Medicine, New York, NY 10001, USA.
Triple negative breast cancer (TNBC) is characterized by the absence of hormones and growth factor receptors. It is typically responsive to anthracycline/taxol-based conventional chemotherapy. However, major therapeutic limitations include systemic toxicity and acquired resistance to chemotherapeutics.
View Article and Find Full Text PDFBiomed Pharmacother
December 2024
Department of molecular oncology, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, Serbia. Electronic address:
Hydroxyurea (hydroxycarbamide, HU) arrests cells in the S-phase by inhibiting ribonucleotide reductase and DNA synthesis, significantly contributing to the release of nitric oxide (NO). We investigated the involvement of inducible NO synthase (NOS2) in the cytostatic effect of HU using in vitro shRNA-induced knockdown of the NOS2 transcript (NOS2) or a specific NOS2 inhibitor (1400W) in human erythroleukemic HEL92.1.
View Article and Find Full Text PDFPharmaceutics
November 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
Targeted delivery of chemotherapeutic agents is a well-established approach to cancer therapy. Antibody-drug conjugates (ADCs) typically carry toxic payloads attached to a tumor-associated antigen-targeting IgG antibody via an enzyme-cleavable linker that releases the drug inside the cell. Aptamers are a promising alternative to antibodies in terms of antigen targeting; however, their polynucleotide nature and smaller size result in a completely different PK/PD profile compared to an IgG.
View Article and Find Full Text PDFDis Model Mech
December 2024
Centre for Regenerative Medicine, Institute for Regeneration and Repair and Edinburgh Cancer Research UK Centre, The University of Edinburgh, Edinburgh EH16 4UU, UK.
The molecular mechanisms controlling the balance of quiescence and proliferation in adult neural stem cells (NSCs) are often deregulated in brain cancers such as glioblastoma multiforme (GBM). Previously, we reported that FOXG1, a forebrain-restricted neurodevelopmental transcription factor, is frequently upregulated in glioblastoma stem cells (GSCs) and limits the effects of cytostatic pathways, in part by repression of the tumour suppressor Foxo3. Here, we show that increased FOXG1 upregulates Foxo6, a more recently discovered FOXO family member with potential oncogenic functions.
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