First signals Bonner, John Tyler; Bonner, John Tyler
2000., 20090911, 2009, 2001, 2001-01-01
eBook
The enormous recent success of molecular developmental biology has yielded a vast amount of new information on the details of development. So much so that we risk losing sight of the underlying ...principles that apply to all development. To cut through this thicket, John Tyler Bonner ponders a moment in evolution when development was at its most basic--the moment when signaling between cells began. Although multicellularity arose numerous times, most of those events happened many millions of years ago. Many of the details of development that we see today, even in simple organisms, accrued over a long evolutionary timeline, and the initial events are obscured. The relatively uncomplicated and easy-to-grow cellular slime molds offer a unique opportunity to analyze development at a primitive stage and perhaps gain insight into how early multicellular development might have started.
The cGAS-STING signalling pathway has emerged as a key mediator of inflammation in the settings of infection, cellular stress and tissue damage. Underlying this broad involvement of the cGAS-STING ...pathway is its capacity to sense and regulate the cellular response towards microbial and host-derived DNAs, which serve as ubiquitous danger-associated molecules. Insights into the structural and molecular biology of the cGAS-STING pathway have enabled the development of selective small-molecule inhibitors with the potential to target the cGAS-STING axis in a number of inflammatory diseases in humans. Here, we outline the principal elements of the cGAS-STING signalling cascade and discuss the general mechanisms underlying the association of cGAS-STING activity with various autoinflammatory, autoimmune and degenerative diseases. Finally, we outline the chemical nature of recently developed cGAS and STING antagonists and summarize their potential clinical applications.
Signaling Pathways in Liver Diseases, 2nd edition focuses on signaling pathways which are particularly important in liver diseases. Recent progress brought hepatology to new frontiers. The increasing ...frequency of surgery on steatotic and cirrhotic liver obliges liver surgeons and hepatologists to understand the molecular mechanisms at play in these situations and how they can be influenced. Better comprehension of the cellular mechanisms participating in liver regeneration, hepato-cellular apoptosis and ischemia/reperfusion inquiry is mirrored by a dramatic increase in complexity. The number and scope of publications is intimidating and difficult for busy individuals to extract a coherent framework. This book will serve as a source of information facilitating the reading of the literature and the planning of trials. Translational medicine implies knowledge of the molecular targets for novel therapeutic strategies. It will furthermore stimulate more research and lead to better exchange between the laboratory, the clinical ward and the operation room.
This book shows the complexity of plant signaling and behavior in an ecological context and is intended to increase our understanding of it. It reflects the multifaceted interactions between plants ...and other organisms that affect their growth and development. In addition it puts emphasis on the effects of plant signaling and behavior on other trophic levels. This field of research is growing and developing rapidly, and new findings are regularly reported. Thus, this book provides a broader view of the field and represents a valuable reference work on the current state of research.
Protein handling, modification and folding in the endoplasmic reticulum (ER) are tightly regulated processes that determine cell function, fate and survival. In several tumour types, diverse ...oncogenic, transcriptional and metabolic abnormalities cooperate to generate hostile microenvironments that disrupt ER homeostasis in malignant and stromal cells, as well as infiltrating leukocytes. These changes provoke a state of persistent ER stress that has been demonstrated to govern multiple pro-tumoural attributes in the cancer cell while dynamically reprogramming the function of innate and adaptive immune cells. Aberrant activation of ER stress sensors and their downstream signalling pathways have therefore emerged as key regulators of tumour growth and metastasis as well as response to chemotherapy, targeted therapies and immunotherapy. In this Review, we discuss the physiological inducers of ER stress in the tumour milieu, the interplay between oncogenic signalling and ER stress response pathways in the cancer cell and the profound immunomodulatory effects of sustained ER stress responses in tumours.
Summary
Reactive oxygen species (ROS) play a key role in the acclimation process of plants to abiotic stress. They primarily function as signal transduction molecules that regulate different pathways ...during plant acclimation to stress, but are also toxic byproducts of stress metabolism. Because each subcellular compartment in plants contains its own set of ROS‐producing and ROS‐scavenging pathways, the steady‐state level of ROS, as well as the redox state of each compartment, is different at any given time giving rise to a distinct signature of ROS levels at the different compartments of the cell. Here we review recent studies on the role of ROS in abiotic stress in plants, and propose that different abiotic stresses, such as drought, heat, salinity and high light, result in different ROS signatures that determine the specificity of the acclimation response and help tailor it to the exact stress the plant encounters. We further address the role of ROS in the acclimation of plants to stress combination as well as the role of ROS in mediating rapid systemic signaling during abiotic stress. We conclude that as long as cells maintain high enough energy reserves to detoxify ROS, ROS is beneficial to plants during abiotic stress enabling them to adjust their metabolism and mount a proper acclimation response.
Significance Statement
Reactive oxygen species (ROS) primarily function as signal transduction molecules that regulate different pathways during acclimation to stress, but are also toxic byproducts of stress metabolism. Different subcellular compartments contain different sets of ROS‐producing and ROS‐scavenging pathways, and thus ROS levels can have different signatures in different cellular compartments. Here we review recent work on ROS and abiotic stress, and propose that different stresses, such as drought, heat, salinity and high light, result in different ROS signatures that determine the specificity of the acclimation response to a particular stress.
Amplification of epidermal growth factor receptor (EGFR) and its active mutant EGFRvIII occurs frequently in glioblastoma (GBM). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted ...therapy with EGFR-tyrosine kinase inhibitors (TKIs) or antibodies has only shown limited efficacy in patients. Here we discuss signaling pathways mediated by EGFR/EGFRvIII, current therapeutics, and novel strategies to target EGFR/EGFRvIII-amplified GBM.
Targeting apoptosis in cancer therapy Carneiro, Benedito A; El-Deiry, Wafik S
Nature reviews. Clinical oncology,
07/2020, Letnik:
17, Številka:
7
Journal Article
Recenzirano
Odprti dostop
For over three decades, a mainstay and goal of clinical oncology has been the development of therapies promoting the effective elimination of cancer cells by apoptosis. This programmed cell death ...process is mediated by several signalling pathways (referred to as intrinsic and extrinsic) triggered by multiple factors, including cellular stress, DNA damage and immune surveillance. The interaction of apoptosis pathways with other signalling mechanisms can also affect cell death. The clinical translation of effective pro-apoptotic agents involves drug discovery studies (addressing the bioavailability, stability, tumour penetration, toxicity profile in non-malignant tissues, drug interactions and off-target effects) as well as an understanding of tumour biology (including heterogeneity and evolution of resistant clones). While tumour cell death can result in response to therapy, the selection, growth and dissemination of resistant cells can ultimately be fatal. In this Review, we present the main apoptosis pathways and other signalling pathways that interact with them, and discuss actionable molecular targets, therapeutic agents in clinical translation and known mechanisms of resistance to these agents.
The mTOR pathway integrates a diverse set of environmental cues, such as growth factor signals and nutritional status, to direct eukaryotic cell growth. Over the past two and a half decades, mapping ...of the mTOR signalling landscape has revealed that mTOR controls biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Given the pathway's central role in maintaining cellular and physiological homeostasis, dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing. In this Review, we highlight recent advances in our understanding of the complex regulation of the mTOR pathway and discuss its function in the context of physiology, human disease and pharmacological intervention.
PDF
