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Cell Metabolism Mar 2012Lipolysis is defined as the catabolism of triacylglycerols stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of... (Review)
Review
Lipolysis is defined as the catabolism of triacylglycerols stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of numerous regulatory proteins and mechanisms have fundamentally changed our perception of lipolysis and its impact on cellular metabolism. New findings that lipolytic products and intermediates participate in cellular signaling processes and that "lipolytic signaling" is particularly important in many nonadipose tissues unveil a previously underappreciated aspect of lipolysis, which may be relevant for human disease.
Topics: Animals; Humans; Lipase; Lipid Metabolism; Lipolysis; Signal Transduction
PubMed: 22405066
DOI: 10.1016/j.cmet.2011.12.018 -
Trends in Plant Science Jan 2017Reactive oxygen species (ROS) are thought to play a dual role in plant biology. They are required for many important signaling reactions, but are also toxic byproducts... (Review)
Review
Reactive oxygen species (ROS) are thought to play a dual role in plant biology. They are required for many important signaling reactions, but are also toxic byproducts of aerobic metabolism. Recent studies revealed that ROS are necessary for the progression of several basic biological processes including cellular proliferation and differentiation. Moreover, cell death-that was previously thought to be the outcome of ROS directly killing cells by oxidation, in other words via oxidative stress-is now considered to be the result of ROS triggering a physiological or programmed pathway for cell death. This Opinion focuses on the possibility that ROS are beneficial to plants, supporting cellular proliferation, physiological function, and viability, and that maintaining a basal level of ROS in cells is essential for life.
Topics: Gene Expression Regulation, Plant; Oxidation-Reduction; Plants; Reactive Oxygen Species; Signal Transduction
PubMed: 27666517
DOI: 10.1016/j.tplants.2016.08.002 -
Biochemia Medica 2014Estrogens have long been known as important regulators of the female reproductive functions; however, our understanding of the role estrogens play in the human body has... (Review)
Review
Estrogens have long been known as important regulators of the female reproductive functions; however, our understanding of the role estrogens play in the human body has changed significantly over the past years. It is now commonly accepted that estrogens and androgens have important functions in both female and male physiology and pathology. This is in part due to the local synthesis and action of estrogens that broadens the role of estrogen signaling beyond that of the endocrine system. Furthermore, there are several different mechanisms through which the three estrogen receptors (ERs), ERα, ERβ and G protein-coupled estrogen receptor 1 (GPER1) are able to regulate target gene transcription. ERα and ERβ are mostly associated with the direct and indirect genomic signaling pathways that result in target gene expression. Membrane-bound GPER1 is on the other hand responsible for the rapid non-genomic actions of estrogens that activate various protein-kinase cascades. Estrogen signaling is also tightly connected with another important regulatory entity, i.e. epigenetic mechanisms. Posttranslational histone modifications, microRNAs (miRNAs) and DNA methylation have been shown to influence gene expression of ERs as well as being regulated by estrogen signaling. Moreover, several coregulators of estrogen signaling also exhibit chromatin-modifying activities further underlining the importance of epigenetic mechanisms in estrogen signaling. This review wishes to highlight the newer aspects of estrogen signaling that exceed its classical endocrine regulatory role, especially emphasizing its tight intertwinement with epigenetic mechanisms.
Topics: Epigenesis, Genetic; Estrogens; Female; Gene Expression Regulation; Humans; Male; Receptors, Estrogen; Signal Transduction; Structure-Activity Relationship; Tissue Distribution
PubMed: 25351351
DOI: 10.11613/BM.2014.035 -
The Plant Journal : For Cell and... Jun 2017Reactive oxygen species (ROS) play a key role in the acclimation process of plants to abiotic stress. They primarily function as signal transduction molecules that... (Review)
Review
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.
Topics: Droughts; Gene Expression Regulation, Plant; Hot Temperature; Light; Plants; Reactive Oxygen Species; Signal Transduction; Sodium Chloride
PubMed: 27801967
DOI: 10.1111/tpj.13299 -
Frontiers in Endocrinology 2020
Topics: Animals; Endocrine System; Endocrine System Diseases; Hormones; Humans; Signal Transduction
PubMed: 33013691
DOI: 10.3389/fendo.2020.00589 -
Frontiers in Immunology 2020Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential... (Review)
Review
Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immune-surveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. cGAS-STING pathway interplays with other innate immune pathways, by which it participates in regulating infection, inflammatory disease, and cancer. The therapeutic approaches targeting this pathway show promise for future translation into clinical applications. Here, we present a review of the important previous works and recent advances regarding the cGAS-STING pathway, and provide a comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states.
Topics: Autophagy; Cell Survival; Cellular Senescence; DNA; Humans; Infections; Inflammation; Interferon Type I; Membrane Proteins; Neoplasms; Nucleotidyltransferases; Signal Transduction
PubMed: 32411126
DOI: 10.3389/fimmu.2020.00615 -
Biological & Pharmaceutical Bulletin 2022The cytokine, transforming growth factor beta (TGF-β), has a history of more than 40 years. TGF-β is secreted by many tumor cells and is associated with tumor growth... (Review)
Review
The cytokine, transforming growth factor beta (TGF-β), has a history of more than 40 years. TGF-β is secreted by many tumor cells and is associated with tumor growth and cancer immunity. The canonical TGF-β signaling pathway, SMAD, controls both tumor metastasis and immune regulation, thereby regulating cancer immunity. TGF-β regulates multiple types of immune cells in tumor microenvironment, including T cells, natural killer (NK) cells, and macrophages. One of the main roles of TGF-β in the tumor microenvironment is the generation of regulatory T cells, which contribute to the suppression of anti-tumor immunity. Because cancer is one of the highest causes of death globally, the discovery of immune checkpoint inhibitors by Honjo and Allison in cancer immunotherapy earned a Nobel Prize in 2018. TGF-β also regulates the levels of immune checkpoints inhibitory receptors on immune cells. Immune checkpoints inhibitors are now being developed along with anti-TGF-β antibody and/or TGF-β inhibitors. More recently, chimeric antigen receptors (CARs) were applied to cancer immunity and tried to combine with TGF-β blockers.
Topics: Gene Expression Regulation, Neoplastic; Humans; Immunotherapy; Neoplasms; Signal Transduction; Transforming Growth Factor beta
PubMed: 35110501
DOI: 10.1248/bpb.b21-00966 -
Journal of Genetics and Genomics = Yi... Oct 2015Signal transduction pathways activated by receptor tyrosine kinases (RTK) play a critical role in many aspects of cell function. Adaptor proteins serve an important... (Review)
Review
Signal transduction pathways activated by receptor tyrosine kinases (RTK) play a critical role in many aspects of cell function. Adaptor proteins serve an important scaffolding function that facilitates key signaling transduction events downstream of RTKs. Recent work integrating both structural and functional genomic approaches has identified several adaptor proteins as new oncogenes. In this review, we focus on the discovery, structure and function, and therapeutic implication of three of these adaptor oncogenes, CRKL, GAB2, and FRS2. Each of the three genes is recurrently amplified in lung adenocarcinoma or ovarian cancer, and is essential to cancer cell lines that harbor such amplification. Overexpression of each gene is able to transform immortalized human cell lines in in vitro or in vivo models. These observations identify adaptor protein as a distinct class of oncogenes and potential therapeutic targets.
Topics: Adaptor Proteins, Signal Transducing; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Signal Transduction
PubMed: 26554907
DOI: 10.1016/j.jgg.2015.09.001 -
BioMed Research International 2015
Topics: Antineoplastic Agents; Humans; Neoplasms; Signal Transduction
PubMed: 26090424
DOI: 10.1155/2015/584170 -
Genes & Development Nov 2020The roles of SPRED proteins in signaling, development, and cancer are becoming increasingly recognized. SPRED proteins comprise an N-terminal EVH-1 domain, a central... (Review)
Review
The roles of SPRED proteins in signaling, development, and cancer are becoming increasingly recognized. SPRED proteins comprise an N-terminal EVH-1 domain, a central c-Kit-binding domain, and C-terminal SROUTY domain. They negatively regulate signaling from tyrosine kinases to the Ras-MAPK pathway. SPRED1 binds directly to both c-KIT and to the RasGAP, neurofibromin, whose function is completely dependent on this interaction. Loss-of-function mutations in SPRED1 occur in human cancers and cause the developmental disorder, Legius syndrome. Genetic ablation of SPRED genes in mice leads to behavioral problems, dwarfism, and multiple other phenotypes including increased risk of leukemia. In this review, we summarize and discuss biochemical, structural, and biological functions of these proteins including their roles in normal cell growth and differentiation and in human disease.
Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Differentiation; Gene Expression Regulation, Developmental; Growth and Development; Humans; Neoplasms; Protein Domains; Signal Transduction
PubMed: 33872193
DOI: 10.1101/gad.341222.120