Search results for "Anaphase"
showing 10 items of 17 documents
An Attachment-Independent Biochemical Timer of the Spindle Assembly Checkpoint.
2017
The spindle assembly checkpoint (SAC) generates a diffusible protein complex that prevents anaphase until all chromosomes are properly attached to spindle microtubules. A key step in SAC initiation is the recruitment of MAD1 to kinetochores, which is generally thought to be governed by the microtubule-kinetochore (MT-KT) attachment status. However, we demonstrate that the recruitment of MAD1 via BUB1, a conserved kinetochore receptor, is not affected by MT-KT interactions in human cells. Instead, BUB1:MAD1 interaction depends on BUB1 phosphorylation, which is controlled by a biochemical timer that integrates counteracting kinase and phosphatase effects on BUB1 into a pulse-generating incohe…
New Functions of APC/C Ubiquitin Ligase in the Nervous System and Its Role in Alzheimer’s Disease
2017
The E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) regulates important processes in cells, such as the cell cycle, by targeting a set of substrates for degradation. In the last decade, APC/C has been related to several major functions in the nervous system, including axon guidance, synaptic plasticity, neurogenesis, and neuronal survival. Interestingly, some of the identified APC/C substrates have been related to neurodegenerative diseases. There is an accumulation of some degradation targets of APC/C in Alzheimer’s disease (AD) brains, which suggests a dysregulation of the protein complex in the disorder. Moreover, recently evidence has been provided for an inactivation o…
Aβ Induces Excitotoxicity Mediated by APC/C-Cdh1 Depletion That Can Be Prevented by Glutaminase Inhibition Promoting Neuronal Survival
2016
AbstractThe E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated by the fizzy-related protein homolog/CDC20-like protein 1 (cdh1) in post-mitotic neurons. Growing evidence suggests that dysregulation of APC/C-Cdh1 is involved in neurodegenerative diseases. Here we show in neurons that oligomers of amyloid beta (Aβ), a peptide related to Alzheimer’s disease, cause proteasome-dependent degradation of cdh1. This leads to a subsequent increase in glutaminase (a degradation target of APC/C-Cdh1), which causes an elevation of glutamate levels and further intraneuronal Ca2+ dysregulation, resulting in neuronal apoptosis. Glutaminase inhibition prevents glutamate excitotoxi…
An overview on anti-tubulin agents for the treatment of lymphoma patients
2020
Anti-tubulin agents constitute a large class of compounds with broad activity both in solid tumors and hematologic malignancies, due to the interference with microtubule dynamics. Since microtubules play crucial roles in the regulation of the mitotic spindles, the interference with their function usually leads to a block in cell division with arrest at the metaphase/anaphase junction of mitosis, followed to apoptosis. This explains the reason why tubulin-binding agents (TBAs) proved to be extremely active in patients with cancer. Several anti-tubulin agents are indicated in the treatment of patients with lymphomas both alone and in combination chemotherapy regimens. The article reviews the …
Separase is a marker for prognosis and mitotic activity in breast cancer
2017
Background: Cancer cell proliferation is a critical feature in classifying and predicting the outcome of breast carcinoma. Separase has a central role in cell cycle progression in unleashing sister-chromatids at anaphase onset. Abnormally functioning separase is known to lead to chromosomal instability. Methods: The study comprises 349 breast carcinoma patients treated in Central Hospital of Central Finland. The prognostic value, role as a proliferation marker and regulatory interactions of separase are evaluated by immunohistochemical and double- and triple-immunofluorescence (IF) detections based on complete clinical data and >22-year follow-up of the patient material. Results: In our mat…
Alternative lengthening of telomeres--an enhanced chromosomal instability in aggressive non-MYCN amplified and telomere elongated neuroblastomas
2010
Telomere length alterations are known to cause genomic instability and influence clinical course in several tumor types, but have been little investigated in neuroblastoma (NB), one of the most common childhood tumors. In the present study, telomere-dependent chromosomal instability and telomere length were determined in six NB cell lines and fifty tumor biopsies. The alternative lengthening of telomeres (ALT) pathway was assayed by scoring ALT-associated promyelocytic leukemia (PML) bodies (APBs). We found a reduced probability of overall survival for tumors with increased telomere length compared to cases with reduced or unchanged telomere length. In non-MYCN amplified tumors, a reduced o…
The autoantigen La/SSB: detection on and uptake by mitotic cells.
1992
Abstract The nuclear autoantigen La, a transcription/termination factor of RNA polymerase III, was recently shown to translocalize to the cell surface of growth-stimulated cells during transition from G0- to G1-phase. Here we describe the staining of living mitotic cells with the anti-La mab La11G7. Moreover, La protein added to cell culture medium was able to enter into synchronized mitotic cells. Uptake was inhibited by the anti-La mab. La protein taken up into prophase cells assembled into a fibrillar network. Taken up by ana/telophase cells, La protein was preferentially transported into the newly forming or formed nuclei. This import allowed us to study directly the intranuclear locali…
The APC/C cofactor Cdh1 prevents replicative stress and p53-dependent cell death in neural progenitors
2013
The E3-ubiquitin ligase APC/C-Cdh1 is essential for endoreduplication but its relevance in the mammalian mitotic cell cycle is still unclear. Here we show that genetic ablation of Cdh1 in the developing nervous system results in hypoplastic brain and hydrocephalus. These defects correlate with enhanced levels of Cdh1 substrates and increased entry into the S phase in neural progenitors. However, cell division is prevented in the absence of Cdh1 due to hyperactivation of cyclin-dependent kinases, replicative stress, induction of p53, G2 arrest and apoptotic death of these progenitor cells. Concomitant ablation of p53 rescues apoptosis but not replicative stress, resulting in the presence of …
Strange vesicles with a homogeneous content in spermatocytes and spermatids of a click beetle, Adelocera murina (Elateridae). A fine structure study
1996
Abstract The restructuring of primary spermatocytes of Adelocera murina, a click beetle, is described using electron microscopy of ultrathin sections. Emphasis is on spherical or rod-shaped cytoplasmic inclusions, invested by a unit membrane. The content of the inclusions is slightly more electron-dense than that of the surrounding cytoplasm and homogeneously textured in most cases. The inclusions are missing in spermatogonia but are abundant in prophase I through anaphase I spermatocytes. Their number declines in telophase I. Very similar elements are associated with the distal ends of the outgrowing flagella in metaphase I through telophase I spermatocytes and form the so-called flagellar…
Microtubule organization and distribution of gamma-tubulin in male meiosis of lepidoptera
1996
Meiotic spindles in males of higher Lepidotera are unusual in that the bulk of the spindle micro-tubules (MTs) ends about halfway between the equatorial plate and the centrosomes in metaphase. It appears worthwhile to determine how the MTs are nucleated, while their pole proximal ends are distant from the centrosomes. To this end, spermatocytes of Phragmatobia fuliginosa (Arctiidae), collected in the field, were double-labeled with antibodies to beta- and gamma-tubulin. The former antibody reveals the entire microtubular cytoskeleton, and the latter is directed against a newly-discovered tublin isoform that is prevalent in microtubule-organizing centers (MTOCs). The immunocytochemical work …