Search results for "Cell Cycle Proteins"
showing 10 items of 127 documents
Acute telomerase components depletion triggers oxidative stress as an early event previous to telomeric shortening
2018
Loss of function of dyskerin (DKC1), NOP10 and TIN2 are responsible for different inheritance patterns of Dyskeratosis congenita (DC; ORPHA1775). They are key components of telomerase (DKC1 and NOP10) and shelterin (TIN2), and play an important role in telomere homeostasis. They participate in several fundamental cellular processes by contributing to Dyskeratosis congenita through mechanisms that are not fully understood. Presence of oxidative stress was postulated to result from telomerase ablation. However, the resulting disturbed redox status can promote telomere attrition by generating a vicious circle, which promotes cellular senescence. This fact prompted us to study if acute loss of …
Palmitoylation is a post-translational modification of Alix regulating the membrane organization of exosome-like small extracellular vesicles.
2018
Abstract Background Virtually all cell types have the capacity to secrete nanometer-sized extracellular vesicles, which have emerged in recent years as potent signal transducers and cell-cell communicators. The multifunctional protein Alix is a bona fide exosomal regulator and skeletal muscle cells can release Alix-positive nano-sized extracellular vesicles, offering a new paradigm for understanding how myofibers communicate within skeletal muscle and with other organs. S-palmitoylation is a reversible lipid post-translational modification, involved in different biological processes, such as the trafficking of membrane proteins, achievement of stable protein conformations, and stabilization…
AMG900 as novel inhibitor of the translationally controlled tumor protein
2020
Abstract Introduction Cancer is one of the leading causes of death worldwide. Classical cytotoxic chemotherapy exerts high side effects and low tumor selectivity. Translationally controlled tumor protein (TCTP) is a target for differentiation therapy, a promising, new therapeutic approach, which is expected to be more selective and less toxic than cytotoxic chemotherapy. The aim of the present investigation was to identify novel TCTP inhibitors. Methods We performed in silico screening and molecular docking using a chemical library of more than 31,000 compounds to identify a novel inhibitor of TCTP. We tested AMG900 in vitro for binding to TCTP by microscale thermophoresis and co-immunoprec…
Chronic Sulforaphane Application Does Not Induce Resistance in Renal Cell Carcinoma Cells.
2018
Background/aim Since the natural compound sulforaphane (SFN) has been shown to stop tumor growth, renal cell carcinoma (RCC) patients often use this drug in addition to their prescribed oncotherapy. The aim of this study was to examine whether resistance to SFN may develop after long-term application. Materials and methods Several RCC cell lines were incubated with SFN for short periods of time (24-72 h) or long periods of time (8 weeks) and cell growth, proliferation, and cell-cycle proteins were analyzed. Results Both short- and long-term application of SFN distinctly reduced RCC cell growth and proliferation. However, differences in the distribution of cells in each phase of the cell cyc…
The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress
2015
The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex migh…
Plasmonic Nanosensors for the Determination of Drug Effectiveness on Membrane Receptors.
2016
We demonstrate the potential of the NanoSPR (nanoscale surface plasmon resonance sensors) method as a simple and cheap tool for the quantitative study of membrane protein–protein interactions. We use NanoSPR to determine the effectiveness of two potential drug candidates that inhibit the protein complex formation between FtsA and ZipA at initial stages of bacterial division. As the NanoSPR method relies on individual gold nanorods as sensing elements, there is no need for fluorescent labels or organic cosolvents, and it provides intrinsically high statistics. NanoSPR could become a powerful tool in drug development, drug delivery, and membrane studies.
Single Particle Plasmon Sensors as Label-Free Technique To Monitor MinDE Protein Wave Propagation on Membranes.
2016
We use individual gold nanorods as pointlike detectors for the intrinsic dynamics of an oscillating biological system. We chose the pattern forming MinDE protein system from Escherichia coli (E. coli), a prominent example for self-organized chemical oscillations of membrane-associated proteins that are involved in the bacterial cell division process. Similar to surface plasmon resonance (SPR), the gold nanorods report changes in their protein surface coverage without the need for fluorescence labeling, a technique we refer to as NanoSPR. Comparing the dynamics for fluorescence labeled and unlabeled proteins, we find a reduction of the oscillation period by about 20%. The absence of photoble…
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…
Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies.
2019
Cohesin complex disruption alters gene expression, and cohesin mutations are common in myeloid neoplasia, suggesting a critical role in hematopoiesis. Here, we explore cohesin dynamics and regulation of hematopoietic stem cell homeostasis and differentiation. Cohesin binding increases at active regulatory elements only during erythroid differentiation. Prior binding of the repressive Ets transcription factor Etv6 predicts cohesin binding at these elements and Etv6 interacts with cohesin at chromatin. Depletion of cohesin severely impairs erythroid differentiation, particularly at Etv6-prebound loci, but augments self-renewal programs. Together with corroborative findings in acute myeloid le…
Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation
2017
MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR- 29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b…