Search results for "Signal"

BAG3 Proteomic Signature under Proteostasis Stress

2020

The multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3) represents a key player in the quality control of the cellular proteostasis network. In response to stress, BAG3 specifically targets aggregation-prone proteins to the perinuclear aggresome and promotes their degradation via BAG3-mediated selective macroautophagy. To adapt cellular homeostasis to stress, BAG3 modulates and functions in various cellular processes and signaling pathways. Noteworthy, dysfunction and deregulation of BAG3 and its pathway are pathophysiologically linked to myopathies, cancer, and neurodegenerative disorders. Here, we report a BAG3 proteomic signature under proteostasis stress. To elucidat…

Reply to ‘Genetic and clinical data reinforce the role of GAS6 and TAM receptors in liver fibrosis’

2016

The Long and Winding Road to Useful Predictive Factors for Anti-EGFR Therapy in Metastatic Colorectal Carcinoma: The KRAS/BRAF Pathway

2010

Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with metastatic colorectal carcinoma. Among patients not carrying activating mutations in the KRAS gene, only a limited number will experience tumor response to these therapeutic agents. The role of BRAF mutations in determining resistance to this treatment is emerging through preclinical and clinical studies. Standardization and validation of laboratory mutation analysis is needed to allow an optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Clinical single-arm and randomized studies were conducted both in first-line and refractory settings to evaluate…

B-Raf Acts via the ROCKII/LIMK/Cofilin Pathway To Maintain Actin Stress Fibers in Fibroblasts

2004

Members of the Raf family of serine/threonine protein kinases have been well studied in a variety of organisms ranging from Drosophila to humans. Three raf homologues (raf-1, B-raf, and A-raf) exist in mammals, while a single prototypic homologue exists in lower organisms. A wealth of genetic and biochemical data have indicated that Raf family members are signaling kinases that are integral components of the conserved Ras/Raf/MEK/ERK signaling cascade. Following activation by Ras-dependent mechanisms, Raf protein kinases act as mitogen-activated protein (MAP) kinase kinase kinases, which phosphorylate and activate the type 1/2 MAP kinase kinases, also known as MEK1/2. These dual-specificity…

Piclamilast inhibits the pro-apoptotic and anti-proliferative responses of A549 cells exposed to H(2)O(2) via mechanisms involving AP-1 activation.

2012

Reactive oxygen species (ROS) are involved in the pathogenesis of many inflammatory diseases such as chronic obstructive pulmonary disease (COPD). They can alter the expression of genes involved in cellular damage by activating transcription factors, including the NF-κB and the activator protein 1 (AP-1). Phosphodiesterase type 4 (PDE4) inhibitors have anti-inflammatory and antioxidant effects, as described in in vivo and in vitro COPD models. This study analysed the effects of piclamilast, a selective PDE4 inhibitor, on modulating the global gene expression profile in A549 cells exposed to H(2)O(2).Changes in gene expression were analysed using high-density Affymetrix microarrays and valid…

Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation

2015

Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PI…

Signal-Processing and Adaptive Prototissue Formation in Metabolic DNA Protocells

2021

Abstract The fundamental life-defining processes in living cells, such as replication, division, adaptation, and tissue formation, take place via intertwined metabolic reaction networks orchestrating downstream signal processing in a confined, crowded environment with high precision. Hence, it is crucial to understand and reenact some of these functions in wholly synthetic cell-like entities (protocells) to envision designing soft-materials with life-like traits. Herein, we report on a programmable all-DNA protocell (PC) composed of a liquid DNA interior and a hydrogel-like shell, harboring DNAzyme active sites in the interior whose catalytic bond-cleaving activity leads to a downstream phe…

Online Closed-Loop Real-Time tES-fMRI for Brain Modulation: Feasibility, Noise/Safety and Pilot Study

2021

AbstractRecent studies suggest that transcranial electrical stimulation (tES) can be performed during functional magnetic resonance imaging (fMRI). The novel approach of using concurrent tES-fMRI to modulate and measure targeted brain activity/connectivity may provide unique insights into the causal interactions between the brain neural responses and psychiatric/neurologic signs and symptoms, and importantly, guide the development of new treatments. However, tES stimulation parameters to optimally influence the underlying brain activity in health and disorder may vary with respect to phase, frequency, intensity and electrode’s montage. Here, we delineate how a closed-loop tES-fMRI study of …

Pterostilbene-induced tumor cytotoxicity: a lysosomal membrane permeabilization-dependent mechanism.

2012

The phenolic phytoalexin resveratrol is well known for its health-promoting and anticancer properties. Its potential benefits are, however, limited due to its low bioavailability. Pterostilbene, a natural dimethoxylated analog of resveratrol, presents higher anticancer activity than resveratrol. The mechanisms by which this polyphenol acts against cancer cells are, however, unclear. Here, we show that pterostilbene effectively inhibits cancer cell growth and stimulates apoptosis and autophagosome accumulation in cancer cells of various origins. However, these mechanisms are not determinant in cell demise. Pterostilbene promotes cancer cell death via a mechanism involving lysosomal membrane …

The role of mucin 1 in respiratory diseases

2020

Recent evidence has demonstrated that mucin 1 (MUC1) is involved in many pathological processes that occur in the lung. MUC1 is a transmembrane protein mainly expressed by epithelial and hematopoietic cells. It has a receptor-like structure, which can sense the external environment and activate intracellular signal transduction pathways through its cytoplasmic domain. The extracellular domain of MUC1 can be released to the external environment, thus acting as a decoy barrier to mucosal pathogens, as well as serving as a serum biomarker for the diagnosis and prognosis of several respiratory diseases such as lung cancer and interstitial lung diseases. Furthermore, bioactivated MUC1-cytoplasmi…