Search results for "Transduction"
showing 10 items of 2149 documents
The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia
2018
Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat …
Vitamin E transport, membrane incorporation and cell metabolism: Is α-tocopherol in lipid rafts an oar in the lifeboat?
2010
International audience; Vitamin E is composed of closely related compounds, including tocopherols and tocotrienols. Studies of the last decade provide strong support for a specific role of alpha-tocopherol in cell signalling and the regulation of gene expression. It produces significant effects on inflammation, cell proliferation and apoptosis that are not shared by other vitamin E isomers with similar antioxidant properties. The different behaviours of vitamin E isomers might relate, at least in part, to the specific effects they exert at the plasma membrane. alpha-Tocopherol is not randomly distributed throughout the phospholipid bilayer of biological membranes, and as compared with other…
NO signaling in plant immunity: A tale of messengers
2015
International audience; Nitric oxide (NO) is a free radical gas involved in a myriad of plant physiological processes including immune responses. How NO mediates its biological effects in plant facing microbial pathogen attack is an unresolved question. Insights into the molecular mechanisms by which it propagates signals reveal the contribution of this simple gas in complex signaling pathways shared with reactive oxygen species (ROS) and the second messenger Ca2+. Understanding of the subtle cross-talks operating between these signals was greatly improved by the recent identification and the functional analysis of proteins regulated through S-nitrosylation, a major NO-dependent post-transl…
Acetic acid and acidification accelerate chronological and replicative aging in yeast
2012
Yeast is widely regarded as one of the most valuable model systems to study aging and particularly the genetics of aging. Researchers have established two different methods to study yeast aging known as the replicative lifespan (RLS) and the chronological lifespan (CLS). These have led to the identification of many mammalian genes that affect aging suggesting that they will continue to shed light on the fundamental biology of aging. In spite of the clear differences underpinning the mitotic cellular potential (RLS) and the survival in the non-dividing mode (CLS), the two models are clearly regulated by partly overlapping regulatory mechanism. This idea is supported by the observation that c…
The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and cilia to regulate ciliogenesis and ciliary protein traffic
2022
ELMODs are a family of three mammalian paralogs that display GTPase activating protein (GAP) activity towards a uniquely broad array of ADP-ribosylation factor (ARF) family GTPases that includes ARF-like (ARL) proteins. ELMODs are ubiquitously expressed in mammalian tissues, highly conserved across eukaryotes, and ancient in origin, being present in the last eukaryotic common ancestor. We described functions of ELMOD2 in immortalized mouse embryonic fibroblasts (MEFs) in the regulation of cell division, microtubules, ciliogenesis, and mitochondrial fusion. Here, using similar strategies with the paralogs ELMOD1 and ELMOD3, we identify novel functions and locations of these cell regulators a…
Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling.
2010
SummaryStem cell division can result in two sibling cells exhibiting differential mitogenic and self-renewing potential. Here, we present evidence that the dual-specificity kinase Dyrk1A is part of a molecular pathway involved in the regulation of biased epidermal growth factor receptor (EGFR) signaling in the progeny of dividing neural stem cells (NSC) of the adult subependymal zone (SEZ). We show that EGFR asymmetry requires regulated sorting and that a normal Dyrk1a dosage is required to sustain EGFR in the two daughters of a symmetrically dividing progenitor. Dyrk1A is symmetrically or asymmetrically distributed during mitosis, and biochemical analyses indicate that it prevents endocyto…
Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone.
2009
We sought to address the fundamental question of how stem cell microenvironments can regulate self-renewal. We found that Notch was active in astroglia-like neural stem cells (NSCs), but not in transit-amplifying progenitors of the murine subependymal zone, and that the level of Notch transcriptional activity correlated with self-renewal and multipotency. Moreover, dividing NSCs appeared to balance renewal with commitment via controlled segregation of Notch activity, leading to biased expression of known (Hes1) and previously unknown (Egfr) Notch target genes in daughter cells. Pigment epithelium-derived factor (PEDF) enhanced Notch-dependent transcription in cells with low Notch signaling,…
Characterization of the Receptor Protein-Tyrosine Kinase Gene from the Marine Sponge Geodia cydonium
1996
Cells are provided with well-defined receptor structures (signal receivers) which interact with their corresponding ligands (signal molecules) and initiate a signal transduction pathway resulting in a change of cellular behavior or metabolism (Stoddard et al. 1992). It is well established that cells from both eukaryotic protists (single-cell organisms) and from Metazoa (multicellular organisms) respond to signals emanating from the extracellular environment. The extracellular signals to which protists respond are mainly nutrients which diffuse to their surfaces, and in most cases cross the cell membrane. In addition, they are able to bind peptide hormones, e.g., insulin or adrenocorticotrop…
Selectivity of pharmacological tools: implications for use in cell physiology. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanis…
2014
Pharmacological inhibitors are frequently used to identify the receptors, receptor subtypes, and associated signaling pathways involved in physiological cell responses. Based on the effects of such inhibitors conclusions are drawn about the involvement of their assumed target or lack thereof. While such inhibitors can be useful tools for a better physiological understanding, their uncritical use can lead to incorrect conclusions. This article reviews the concept of inhibitor selectivity and its implication for cell physiology. Specifically, we discuss the implications of using inhibitor vs. activator approaches, issues of direct vs. indirect pathway modulation, implications of inverse agoni…
Delayed ageing through damage protection by the Arf/p53 pathway.
2007
The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These obser…