Emerging Roles of Pleckstrin-2 Beyond Cell Spreading.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang G
PROVIDER: S-EPMC8637889 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Inhibitor of DNA-binding/differentiation (Id) proteins, a family of helix-loop-helix (HLH) proteins that includes four members of Id1 to Id4 in mammalian cells, are critical for regulating cell growth, differentiation, senescence, cell cycle progression, and increasing angiogenesis and vasculogenesis, as well as accelerating the ability of cell migration. Alzheimer's disease (AD), the most common neurodegenerative disease in the adult population, manifests the signs of cognitive decline, behavioral changes, and functional impairment. The underlying mechanisms for AD are not well-clarified yet, but the aggregation of amyloid-beta peptides (A?s), the major components in the senile plaques observed in AD brains, contributes significantly to the disease progression. Emerging evidence reveals that aberrant cell cycle reentry may play a central role in A?-induced neuronal demise. Recently, we have shown that several signaling mediators, including Id1, hypoxia-inducible factor-1 (HIF-1), cyclin-dependent kinases-5 (CDK5), and sonic hedgehog (Shh), may contribute to A?-induced cell cycle reentry in postmitotic neurons; furthermore, Id1 and CDK5/p25 mutually antagonize the expression/activity of each other. Therefore, Id proteins may potentially have clinical applications in AD. In this review article, we introduce the underlying mechanisms for cell cycle dysregulation in AD and present some examples, including our own studies, to show different aspects of Id1 in terms of cell cycle reentry and other signaling that may be crucial to alter the neuronal fates in this devastating neurodegenerative disease. A thorough understanding of the underlying mechanisms may provide a rationale to make an earlier intervention before the occurrence of cell cycle reentry and subsequent apoptosis in the fully differentiated neurons during the progression of AD or other neurodegenerative diseases.
| S-EPMC7409121 | biostudies-literature
Project description:Metallothioneins (MTs) are low molecular weight, cysteine-rich, metal-binding proteins whose precise biological roles have not been fully characterized. Existing evidence implicated MTs in heavy metal detoxification, metal ion homeostasis and antioxidant defense. MTs were thus categorized as protective effectors that contribute to cellular homeostasis and survival. This view has, however, been challenged by emerging evidence in different medical fields revealing novel pathophysiological roles of MTs, including inflammatory bowel disease, neurodegenerative disorders, carcinogenesis and diabetes. In the present focused review, we discuss the evidence for the role of MTs in pancreatic beta-cell biology and insulin secretion. We highlight the pattern of specific isoforms of MT gene expression in rodents and human beta-cells. We then discuss the mechanisms involved in the regulation of MTs in islets under physiological and pathological conditions, particularly type 2 diabetes, and analyze the evidence revealing adaptive and negative roles of MTs in beta-cells and the potential mechanisms involved. Finally, we underscore the unsettled questions in the field and propose some future research directions.
| S-EPMC7996892 | biostudies-literature
Project description:Troponin is a heterotrimeric Ca2+-binding protein that has a well-established role in regulating striated muscle contraction. However, mounting evidence points to novel cellular functions of troponin, with profound implications in cancer, cardiomyopathy pathogenesis and skeletal muscle aging. Here, we highlight the non-canonical roles and aberrant expression patterns of troponin beyond the sarcomeric milieu. Utilizing bioinformatics tools and online databases, we also provide pathway, subcellular localization, and protein-protein/DNA interaction analyses that support a role for troponin in multiple subcellular compartments. This emerging knowledge challenges the conventional view of troponin as a sarcomere-specific protein exclusively involved in muscle contraction and may transform the way we think about sarcomeric proteins, particularly in the context of human disease and aging.
| S-EPMC5787451 | biostudies-literature
Project description:Enhancers are regulatory DNA elements that dictate the spatial and temporal patterns of gene expression during development. Recent evidence suggests that the distinct chromatin features of enhancer regions provide the permissive landscape required for the differential access of diverse signalling molecules that drive cell-specific gene expression programmes. The epigenetic patterning of enhancers occurs before cell fate decisions, suggesting that the epigenetic information required for subsequent differentiation processes is embedded within the enhancer element. Lineage studies indicate that the patterning of enhancers might be regulated by the intricate interplay between DNA methylation status, the binding of specific transcription factors to enhancers and existing histone modifications. In this review, we present insights into the mechanisms of enhancer function, which might ultimately facilitate cell reprogramming strategies for use in regenerative medicine.
| S-EPMC3343362 | biostudies-other
Project description:Cytosine methylation is the major epigenetic modification of metazoan DNA. Although there is strong evidence that active DNA demethylation occurs in animal cells, the molecular details of this process are unknown. The recent discovery of the TET protein family (TET1-3) 5-methylcytosine hydroxylases has provided a new entry point to reveal the identity of the long-sought DNA demethylase. Here, we review the recent progress in understanding the function of TET proteins and 5-hydroxymethylcytosine (5hmC) through various biochemical and genomic approaches, the current evidence for a role of 5hmC as an early intermediate in active DNA demethylation and the potential functions of TET proteins and 5hmC beyond active DNA demethylation. We also discuss how future studies can extend our knowledge of this novel epigenetic modification.
| S-EPMC3219536 | biostudies-literature
Project description:Maintenance of genome stability is a crucial priority for any organism. To meet this priority, robust signalling networks exist to facilitate error-free DNA replication and repair. These signalling cascades are subject to various regulatory post-translational modifications that range from simple additions of chemical moieties to the conjugation of ubiquitin-like proteins (UBLs). Interferon Stimulated Gene 15 (ISG15) is one such UBL. While classically thought of as a component of antiviral immunity, ISG15 has recently emerged as a regulator of genome stability, with key roles in the DNA damage response (DDR) to modulate p53 signalling and error-free DNA replication. Additional proteomic analyses and cancer-focused studies hint at wider-reaching, uncharacterised functions for ISG15 in genome stability. We review these recent discoveries and highlight future perspectives to increase our understanding of this multifaceted UBL in health and disease.
| S-EPMC7698331 | biostudies-literature
Project description:Cell migration is a key process in health and disease. In the last decade an increasing attention is given to chromatin organization in migrating cells. In various types of cells induction of migration leads to a global increase in heterochromatin levels. Heterochromatin is required for optimal cell migration capabilities, since various interventions with heterochromatin formation impeded the migration rate of numerous cell types. Heterochromatin supports the migration process by affecting both the mechanical properties of the nucleus as well as the genetic processes taking place within it. Increased heterochromatin levels elevate nuclear rigidity in a manner that allows faster cell migration in 3D environments. Condensed chromatin and a more rigid nucleus may increase nuclear durability to shear stress and prevent DNA damage during the migration process. In addition, heterochromatin reorganization in migrating cells is important for induction of migration-specific transcriptional plan together with inhibition of many other unnecessary transcriptional changes. Thus, chromatin organization appears to have a key role in the cellular migration process.
| S-EPMC7266953 | biostudies-literature
Project description:Non-apoptotic regulated cell death (RCD) is essential to maintain organismal homeostasis and may be aberrantly activated during certain pathological states. Lipids are emerging as key components of several non-apoptotic RCD pathways. For example, a direct interaction between membrane phospholipids and the pore-forming protein mixed lineage kinase domain-like (MLKL) is needed for the execution of necroptosis, while the oxidative destruction of membrane polyunsaturated fatty acids (PUFAs), following the inactivation of glutathione peroxidase 4 (GPX4), is a requisite gateway to ferroptosis. Here, we review the roles of lipids in the initiation and execution of these and other forms of non-apoptotic cell death. We also consider new technologies that are allowing for the roles of lipids and lipid metabolism in RCD to be probed in increasingly sophisticated ways. In certain cases, this new knowledge may enable the development of therapies that target lipids and lipid metabolic processes to enhance or suppress specific non-apoptotic RCD pathways.
| S-EPMC5399169 | biostudies-literature
Project description:BackgroundPhosphoenolpyruvate carboxykinase (PCK) has been almost exclusively recognized as a critical enzyme in gluconeogenesis, especially in the liver and kidney. Accumulating evidence has shown that the enhanced activity of PCK leads to increased glucose output and exacerbation of diabetes, whereas the defects of PCK result in lethal hypoglycemia. Genetic mutations or polymorphisms are reported to be related to the onset and progression of diabetes in humans.Scope of reviewRecent studies revealed that the PCK pathway is more complex than just gluconeogenesis, depending on the health or disease condition. Dysregulation of PCK may contribute to the development of obesity, cardiac hypertrophy, stroke, and cancer. Moreover, a regulatory network with multiple layers, from epigenetic regulation, transcription regulation, to posttranscription regulation, precisely tunes the expression of PCK. Deciphering the molecular basis that regulates PCK may pave the way for developing practical strategies to treat metabolic dysfunction.Major conclusionsIn this review, we summarize the metabolic and non-metabolic roles of the PCK enzyme in cells, especially beyond gluconeogenesis. We highlight the distinct functions of PCK isoforms (PCK1 and PCK2), depict a detailed network regulating PCK's expression, and discuss its clinical relevance. We also discuss the therapeutic potential targeting PCK and the future direction that is highly in need to better understand PCK-mediated signaling under diverse conditions.
| S-EPMC8190478 | biostudies-literature
Project description:Getah virus (GETV) is a zoonotic virus transmitted by mosquitoes, belonging to the Togaviridae family, Alphavirus genus. It was first isolated from mosquitoes in Malaysia in 1955, being widespread in island countries in the South Pacific region. Since the beginning of the 21st century, GETV expanded its range and geographical distribution from low-latitude tropical regions to 60° north latitude, being isolated from 17 different species of mosquitoes belonging to five genera of Culicidae (Culex, Anopheles, Armigeres, Aedes and Mansonia), as well as from midges in Eurasia. Molecular genetic evolution analysis revealed large molecular differences between the mosquitoes currently circulating Eurasia and those in the South Pacific in 1950s. The number of disease outbreaks caused by GETV in animals is increasing alongside the types of animals infected, from horses and pigs to cattle, blue foxes and red pandas. The disease burden is severely underestimated, and the economic cost to livestock production remains unknown. Herein, we review GETV temporal and spatial distribution, molecular genetic evolution, transmission and data on disease outbreaks. This work provides a reference for public health workers engaged in GETV research and zoonotic disease prevention and control.
| S-EPMC9416625 | biostudies-literature