Search results for " signaling."

STRIPAK Members Orchestrate Hippo and Insulin Receptor Signaling to Promote Neural Stem Cell Reactivation

2019

Summary Adult stem cells reactivate from quiescence to maintain tissue homeostasis and in response to injury. How the underlying regulatory signals are integrated is largely unknown. Drosophila neural stem cells (NSCs) also leave quiescence to generate adult neurons and glia, a process that is dependent on Hippo signaling inhibition and activation of the insulin-like receptor (InR)/PI3K/Akt cascade. We performed a transcriptome analysis of individual quiescent and reactivating NSCs harvested directly from Drosophila brains and identified the conserved STRIPAK complex members mob4, cka, and PP2A (microtubule star, mts). We show that PP2A/Mts phosphatase, with its regulatory subunit Widerbors…

European contribution to the study of ROS : A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

2017

WOS: 000410470000009

The Role of p53 Signaling in Colorectal Cancer.

2021

Simple Summary The transcription factor p53 is a crucial tumor suppressor that regulates diverse cellular responses to protect against cancer development. Deactivating p53 signaling either by altering p53 regulators or by p53 mutations occurs frequently in human colorectal carcinoma (CRC). Forty-three percent of CRCs harbor p53 mutations that reduce wild-type p53 tumor suppressor activity and often provide neo-morphic functions, which contribute to tumorigenesis. In this review, we summarize wild-type p53 signaling, how it can be deregulated in CRC, and the functional and phenotypical effects of p53 mutations. We also discuss current therapeutic strategies of targeting p53. Abstract The tra…

More than a pore: How voltage-gated calcium channels act on different levels of neuronal communication regulation.

2021

ABSTRACT Voltage-gated calcium channels (VGCCs) represent key regulators of the calcium influx through the plasma membrane of excitable cells, like neurons. Activated by the depolarization of the membrane, the opening of VGCCs induces very transient and local changes in the intracellular calcium concentration, known as calcium nanodomains, that in turn trigger calcium-dependent signaling cascades and the release of chemical neurotransmitters. Based on their central importance as concierges of excitation-secretion coupling and therefore neuronal communication, VGCCs have been studied in multiple aspects of neuronal function and malfunction. However, studies on molecular interaction partners …

2013

Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also for long-term survival of axons. Degeneration of axons occurs in several human myelin diseases, however the molecular mechanisms of axon-glia communication maintaining axon integrity are poorly understood. Here, we describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. We show that activity-dependent release of the neurotransmitter glutamate triggers oligodendroglial exosome secretion mediated by Ca2+ entry through oligodendroglial NMDA and AMPA recep…

Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down-Regulation of CXCL12-Induced T Cell Migration

2015

Pantethine, a natural low-molecular-weight thiol, shows broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We showed recently that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, wit…

2020

Over the last decade, the E3-ubiquitine ligases from IAP (Inhibitor of Apoptosis) family have emerged as potent regulators of immune response. In immune cells, they control signaling pathways driving differentiation and inflammation in response to stimulation of tumor necrosis factor receptor (TNFR) family, pattern-recognition receptors (PRRs), and some cytokine receptors. They are able to control the activity, the cellular fate, or the stability of actors of signaling pathways, acting at different levels from components of receptor-associated multiprotein complexes to signaling effectors and transcription factors, as well as cytoskeleton regulators. Much less is known about ubiquitination …

The Hippo Show Must Go On: YAP Activation as a Therapeutic Strategy in Colorectal Cancer

2020

The role of Hippo pathway in colorectal cancer (CRC) initiation and progression has been controversial. In this issue of Cell Stem Cell, Cheung et al. (2020) shed new light on a distinct function of the transcriptional co-activator YAP as a tumor suppressor and Wnt pathway inhibitor in CRC.

Advanced mechanotherapy: Biotensegrity  for governing metastatic tumor cell fate via modulating the extracellular matrix.

2021

Mechano-transduction is the procedure of mechanical stimulus translation via cells, among substrate shear flow, topography, and stiffness into a biochemical answer. TAZ and YAP are transcriptional coactivators which are recognized as relay proteins that promote mechano-transduction within the Hippo pathway. With regard to healthy cells in homeostasis, mechano-transduction regularly restricts proliferation, and TAZ and YAP are totally inactive. During cancer development a YAP/TAZ - stimulating positive response loop is formed between the growing tumor and the stiffening ECM. As tumor developments, local stromal and cancerous cells take advantage of mechanotransduction to enhance proliferatio…

Interfering with MIF-CD74 signalling on macrophages and dendritic cells with a peptide-based approach restores the immune response against metastatic…

2018

ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in m…