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Topic Review
Hypoxia-Inducible Factor-1α
Aging is one of the hottest topics in biomedical research. Advances in research and medicine have helped to preserve human health, leading to an extension of life expectancy. However, the extension of life is an irreversible process accompanied by the development of aging-related conditions such as weakness, slower metabolism, and stiffness of vessels. It also debated that aging can be considered an actual disease with aging-derived comorbidities, including cancer or cardiovascular disease. Currently, cardiovascular disorders, including atherosclerosis, are considered premature aging and represent the first causes of death in developed countries, accounting for 31% of annual deaths globally. Emerging evidence has identified hypoxia-inducible factor-1α as a critical transcription factor with an essential role in aging-related pathology, in particular, regulating cellular senescence associated with cardiovascular aging.
  • 684
  • 04 Aug 2021
Topic Review
RNA Modifications in Translation Fidelity
RNA modifications play an essential role in determining RNA fate. Recent studies have revealed the effects of such modifications on all steps of RNA metabolism. These modifications range from the addition of simple groups, such as methyl groups, to the addition of highly complex structures, such as sugars. Their consequences for translation fidelity are not always well documented. Unlike the well-known m6A modification, they are thought to have direct effects on either the folding of the molecule or the ability of tRNAs to bind their codons.
  • 684
  • 19 Nov 2021
Topic Review
JNK Pathway in CNS Pathologies
The c-Jun N-terminal kinase (JNK) signalling pathway is a conserved response to a wide range of internal and external cellular stress signals.
  • 684
  • 19 Apr 2021
Topic Review
Control of Protein Synthesis by ERdj1, ERdj2, ERdj6
The endoplasmic reticulum (ER) of mammalian cells is the central organelle for the maturation and folding of transmembrane proteins and for proteins destined to be secreted into the extracellular space. The proper folding of target proteins is achieved and supervised by a complex endogenous chaperone machinery. BiP, a member of the Hsp70 protein family, is the central chaperone in the ER. The chaperoning activity of BiP is assisted by ER-resident DnaJ (ERdj) proteins due to their ability to stimulate the low, intrinsic ATPase activity of BiP. Besides their co-chaperoning activity, ERdj proteins also regulate and tightly control the translation, translocation, and degradation of proteins. Three ERdj co-chaperones, ERdj1, ERdj2, and ERdj6, are functionally involved in the control of translation and translocation of ER target proteins. 
  • 684
  • 28 Jul 2022
Topic Review
TKS4 and TKS5 Scaffold Proteins
Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development. Furthermore, TKS4 has also been implicated in the regulation of homeostasis of mature adipose and bone tissue.
  • 683
  • 19 Jan 2021
Topic Review
Actin-Binding Proteins in Cardiac Hypertrophy
Actin participates in the formation of highly differentiated myofibrils under the regulation of actin-binding proteins (ABPs), which provides a structural basis for the contractile function and morphological change in cardiomyocytes.
  • 683
  • 22 Nov 2022
Topic Review
Small Ras GTPases in Fungi
Monomeric GTPases, which belong to the Ras superfamily, are small proteins involved in many biological processes. The most studied families are Ras, Rho, Rab, Ran, Arf, and Miro, and recently, a new family named Big Ras GTPases was reported. As a general rule, the proteins of all families have five characteristic motifs (G1–G5), and some specific features for each family have been described. The main functions described for monomeric GTPases in fungi include morphogenesis, secondary metabolism, vesicle trafficking, and virulence.
  • 683
  • 21 Jun 2021
Topic Review
GSK-3 and Tau
Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine kinase with a plethora of substrates. As a modulator of several cellular processes, GSK-3 has a central position in cell metabolism and signaling, with important roles both in physiological and pathological conditions. GSK-3 has been associated with a number of human disorders, such as neurodegenerative diseases including Alzheimer’s disease (AD). GSK-3 contributes to the hyperphosphorylation of tau protein, the main component of neurofibrillary tangles (NFTs), one of the hallmarks of AD. GSK-3 is further involved in the regulation of different neuronal processes that are dysregulated during AD pathogenesis, such as the generation of amyloid-β (Aβ) peptide or Aβ-induced cell death, axonal transport, cholinergic function, and adult neurogenesis or synaptic function. In this review, we will summarize recent data about GSK-3 involvement in these processes contributing to AD pathology, mostly focusing on the crucial interplay between GSK-3 and tau protein. We further discuss the current development of potential AD therapies targeting GSK-3 or GSK-3 phosphorylated tau. 
  • 682
  • 11 May 2021
Topic Review
Restoring Proliferation Competence in Terminally Differentiated Myotubes
Terminally differentiated cells are classically defined as specialized cells that have irreversibly lost their ability to proliferate (postmitotic state). Skeletal muscle myotubes are a model system to study terminal differentiation, more amenable than other terminally differentiated histotypes to experimental investigation. Arguably, the fundamental mechanisms underlying the postmitotic state should be shared by most TD cell types.
  • 682
  • 19 Oct 2021
Topic Review
Vasculogenic Mimicry in Breast Cancer
In solid tumors, vasculogenic mimicry (VM) is the formation of vascular structures by cancer cells, allowing to generate a channel-network able to transport blood and tumor cells. While angiogenesis is undertaken by endothelial cells, VM is assumed by cancer cells. Besides the participation of VM in tumor neovascularization, the clinical relevance of this process resides in its ability to favor metastasis and to drive resistance to antiangiogenic therapy. VM occurs in many tumor types, including breast cancer, where it has been associated with a more malignant phenotype, such as triple-negative and HER2-positive tumors. The latter may be explained by known drivers of VM, like hypoxia, TGFB, TWIST1, EPHA2, VEGF, matrix metalloproteinases, and other tumor microenvironment-derived factors, which altogether induce the transformation of tumor cells to a mesenchymal phenotype with a high expression rate of stemness markers.
  • 682
  • 29 Mar 2022
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