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Topic Review
Deltex Proteins Structural and Functional Features
Deltex (DTX) proteins have been considered putative E3 ligases, based on the presence of an E3 RING domain in their protein coding sequence. The human DTX family includes DTX1, DTX2, DTX3, DTX3L and DTX4. Despite the fact that people's knowledge of this class of E3-ubiquitin ligases is still at an early stage, the understanding of their role in oncogenesis is beginning to unfold.
  • 866
  • 17 Jul 2023
Topic Review
Targeting Cell Surface GRP78 in Cancer
The 78-kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone that plays a crucial role in protein folding homeostasis by regulating the unfolded protein response (UPR). In tumour cells, GRP78 is present at the cell surface, where it functions as a signalling receptor involved in numerous proapoptotic and apoptotic pathways that contribute to cancer cell proliferation and metastasis. As such, novel therapeutic strategies that target cell surface GRP78 in the treatment of several human cancers is highlighted.
  • 866
  • 01 Jul 2022
Topic Review
Direct and Indirect Myc Regulation by Mitotic Kinases
c-Myc and the other protein family members (i.e., N-Myc and L-Myc), collectively known as “Myc”, are ubiquitous basic helix–loop–helix–leucine zipper (bHLH-LZ) transcription factors that are critical for several cellular processes during cancer genesis and progression. The importance of kinases in Myc regulation goes beyond their ability to phosphorylate the protein. Some kinases can also indirectly affect Myc protein stability by inducing the degradation of the ubiquitin ligase (PLK1 and PKA). Additionally, some kinases physically interact with Myc, protecting it from proteasomal degradation, such as Aurora-A in neuroblastoma.
  • 866
  • 08 Mar 2023
Topic Review
Mechanisms of Cathepsins in Non-Alcoholic Fatty Liver Disease
Cathepsins are lysosomal proteases that are essential to maintain cellular physiological homeostasis and are involved in multiple processes, such as immune and energy regulation. Cathepsins have also been involved in pathological situations, especially when they are secreted and enter the extracellular space. Non-alcoholic fatty liver disease (NASH) is a condition in which the livers of patients are afflicted by steatosis and inflammation. Cathepsins have been found to be involved in the pathology of NASH, through acting in apoptosis, metabolism and immunity. 
  • 865
  • 08 Oct 2022
Topic Review
Cytokines in Schizophrenia
Schizophrenia is a chronic mental disorder with a complex etiopathogenesis, which involves both congenital and environmental factors. It leads to neurodegenerative changes in the central nervous system (CNS) and a significant impairment of social functioning. Its lifetime incidence has been estimated at 7.1 per 1000 people, and the male to female risk ratio is 1.4:1.
  • 864
  • 07 Dec 2021
Topic Review
The Role of GRP78 in Cancer Stemness
Cancer stemness is proposed to be the main cause of metastasis and tumor relapse after conventional therapy due to the main properties of cancer stem cells. These include unlimited self-renewal, the low percentage in a cell population, asymmetric/symmetric cell division, and the hypothetical different nature for absorbing external substances. As the mechanism of how cancer stemness is maintained remains unknown, further investigation into the basic features of cancer stemness is required. Many articles demonstrated that glucose-regulated protein 78 (GRP78) plays a key role in cancer stemness, suggesting that this molecule is feasible for targeting cancer stem cells.
  • 864
  • 15 Jul 2022
Topic Review
Lipid Droplets in Yeast during Stress and Aging
The baker’s yeast Saccharomyces cerevisiae is a valuable tool for aging research, as many aging- and disease-associated pathways such as DNA repair mechanisms, lipostasis, proteostasis, oxidative stress responses, regulated cell death, nutrient signaling, autophagy, and regulation of the cell cycle are evolutionarily conserved to a high degree. Lipid droplets (LDs) are evolutionary conserved structures that were mentioned for the first time by Van Leeuwenhoek in 1674, but their reassessment as autonomous organelles with important key roles in lipid and energy metabolism occurred many years later. LDs originate from the endoplasmic reticulum (ER). In the first step, neutral lipids are synthesized at the ER and are redirected into the bilayer, leading to an aggregation of the highly motile lipids. Emerging evidence suggests that LDs also fulfil impotant functions during aging and in protein homeostasis.
  • 862
  • 12 Oct 2023
Topic Review
Spatiotemporal Distribution of VPS13A in the Mouse Brain
Loss-of-function mutations in the human vacuolar protein sorting 13 homolog A (VPS13A) gene cause Chorea-acanthocytosis (ChAc). As very little is known about the VPS13A expression in the brain, The main objective of this work was to assess for the first time the spatiotemporal distribution of VPS13A in the mouse brain. Understanding the distinct expression pattern of VPS13A provides relevant information to unravel pathophysiological hallmarks of ChAc.
  • 861
  • 14 Jan 2022
Topic Review
Mammalian Circadian Rhythms and Ubiquitin Ligases
Circadian clocks evolved to enable organisms to anticipate and prepare for periodic environmental changes driven by the day–night cycle. This internal timekeeping mechanism is built on autoregulatory transcription–translation feedback loops that control the rhythmic expression of core clock genes and their protein products. The levels of clock proteins rise and ebb throughout a 24-h period through their rhythmic synthesis and destruction. In the ubiquitin–proteasome system, the process of polyubiquitination, or the covalent attachment of a ubiquitin chain, marks a protein for degradation by the 26S proteasome. The process is regulated by E3 ubiquitin ligases, which recognize specific substrates for ubiquitination.
  • 861
  • 21 Sep 2022
Topic Review
Palmitoylation in Aging and Diseases with Cognitive Decline
Protein lipidation is a common post-translational modification of proteins that plays an important role in human physiology and pathology. One form of protein lipidation, S-palmitoylation, involves the addition of a 16-carbon fatty acid (palmitate) onto proteins. This reversible modification may affect the regulation of protein trafficking and stability in membranes. From multiple experimental studies, a picture emerges whereby protein S-palmitoylation is a ubiquitous yet discrete molecular switch enabling the expansion of protein functions and subcellular localization in minutes to hours. Neural tissue is particularly rich in proteins that are regulated by S-palmitoylation.
  • 861
  • 23 Apr 2023
Topic Review
Ultrastructural Features of the Blood-Brain Barrier
The blood-brain barrier (BBB) is a dynamic barrier separating neurocytes and brain tissues from blood that is extremely sealed and strictly regulated by transporters such as aquaporin-4 (AQP-4), glucose transporter (GLUT), and specialized tight junctional complexes (TJCs) including tight junctions (TJs), adherens junctions (AJs), and Zonulae occludens (ZOs). With specifically selective transcellular and paracellular permeability, the BBB maintains a homeostatic microenvironment to protect the central nervous system (CNS).
  • 861
  • 27 Jul 2023
Topic Review
COVID-19 effect in Stem cells
The new strain of coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) emerged in 2019 and hence is often referred to as coronavirus disease 2019 (COVID-19). This disease causes hypoxic respiratory failure and acute respiratory distress syn-drome (ARDS), and is considered as the cause of a global pandemic. Very limited reports in addi-tion to ex vivo model systems are available to understand the mechanism of action of this virus, which can be used for testing of any drug efficacy against virus infectivity. COVID-19 induces tissue stem cell loss, resulting inhibition of epithelial repair followed by inflammatory fibrotic con-sequences. Development of clinically relevant models is important to examine the impact of the COVID-19 virus in tissue stem cells among different organs.
  • 860
  • 22 Jan 2021
Topic Review
Nurse-Like Cells and CLL-B Cells
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries and is an example of hematological disease where cooperation between genetic defects and tumor microenvironmental interaction is involved in pathogenesis. CLL is a disease that is considered as “addicted to the host”; indeed, the crosstalk between leukemic cells and the tumor microenvironment is essential for leukemic clone maintenance supporting CLL cells’ survival, proliferation, and protection from drug-induced apoptosis. CLL cells are not innocent bystanders but actively model and manipulate the surrounding microenvironment to their own advantage. Besides the different players involved in this crosstalk, nurse-like cells (NLC) resemble features related to leukemia-associated macrophages with an important function in preserving CLL cell survival and supporting an immunosuppressive microenvironment.
  • 860
  • 14 May 2021
Topic Review
Myelin Basic Protein Interaction Landscape
Intrinsically disordered myelin basic protein (MBP) is one of the key autoantigens in autoimmune neurodegeneration and multiple sclerosis particularly. MBP is highly positively charged and lacks a distinct structure in solution, and therefore its intracellular partners are still mostly enigmatic. Here authors used combination of formaldehyde-induced cross-linking followed by immunoprecipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the interaction network of MBP in mammalian cells and provide the list of potential MBP interacting proteins.
  • 860
  • 15 Nov 2021
Topic Review
Exosomes to Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) represents an aggressive and heterogenous group of cancers whose pathologies remain largely unresolved. Exosomes are a subtype of extracellular vesicles secreted by a variety of cells that have begun to spark significant interest in their roles in cancer. As membranous vesicles, spanning from 30–150 nm in diameter, exosomes mediate the transport of various molecules, such as proteins, nucleic acids, and lipids, intercellularly throughout the body. In doing so, exosomes not only act to deliver materials to cancer cells but also as signals that can confer their progression. Accumulating evidence shows the direct correlation between exosomes and the aggressiveness of HNSCC. 
  • 860
  • 24 Nov 2021
Topic Review
GH/IGF Axis
The GH/IGF axis is a major regulator of bone formation and resorption and is essential to the achievement of normal skeleton growth and homeostasis.
  • 859
  • 28 Jul 2021
Topic Review
Intratumoral Heterogeneity and Concept of Cancer Stem Cells
Cancer stem cells (CSCs) present in many tumors are an example of intratumoral heterogeneity of great importance. The original concept of CSCs emerged on the basis of the stem cell theory in its original form and on the reports about the exclusive ability of tumor cells expressing stem cell markers to induce tumor growth.The modern concept of CSCs has been updated by introducing the concept of the cells-of-origin of tumors and according to data obtained by genetic analysis combined with CSC-associated marker profiling and lineage tracing analysis.
  • 859
  • 01 Dec 2022
Topic Review
Regulatory T Cells in Primary Sjögren’s Syndrome
Regulatory T cells (Tregs) play a key role in maintaining immune balance and regulating the loss of self-tolerance mechanisms in various autoimmune diseases, including primary Sjögren’s syndrome (pSS). With the development of pSS primarily in the exocrine glands, lymphocytic infiltration occurs in the early stages, mainly due to activated CD4+ T cells.
  • 857
  • 15 May 2023
Topic Review
Adipose-Derived Extracellular Vesicles Could Promote Metabolic Adaptation
Extracellular vesicles (EVs) are nanoparticles secreted by cells under physiological and pathological conditions, such as metabolic diseases. In this context, EVs are considered potential key mediators in the physiopathology of obesity. It has been reported that EVs derived from adipose tissue (ADEVs) contribute to the development of a local inflammatory response that leads to adipose tissue dysfunction. In addition, it has been proposed that EVs are associated with the onset and progression of several obesity-related metabolic diseases such as insulin resistance. In particular, characterizing the molecular fingerprint of obesity-related ADEVs can provide a bigger picture that better reflects metabolic adaptation though PI3K/Akt/mTOR.
  • 857
  • 20 Jun 2022
Topic Review
Role of lncRNA in Cancer
Here, we summarize several studies of lncRNAs SNPs relevant to chemotherapy responses to further clarify the potential of lncRNAs as potential biomarkers of cancer risk and predictors of drug resistance as well as toxicity.
  • 856
  • 15 Jun 2021
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