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Topic Review
Synthetic Vulnerabilities in the KRAS Pathway
Mutations in Kristen Rat Sarcoma viral oncogene (KRAS) are among the most frequent gain-of-function genetic alterations in human cancer. Most KRAS-driven cancers depend on its sustained expression and signaling. Despite spectacular recent success in the development of inhibitors targeting specific KRAS alleles, the discovery and utilization of effective directed therapies for KRAS-mutant cancers remains a major unmet need.
  • 786
  • 24 Jun 2022
Topic Review
Poly(ADP-ribose) Polymerase 1
Poly(ADP-ribose) (PAR) Polymerase 1 (PARP-1), also known as ADP-ribosyl transferase with diphtheria toxin homology 1 (ARTD-1), is a critical player in DNA damage repair, during which it catalyzes the ADP ribosylation of self and target enzymes. While the nuclear localization of PARP-1 has been well established, recent studies also suggest its mitochondrial localization.
  • 786
  • 28 Aug 2023
Topic Review
Heat Shock Protein 27
Heat shock proteins (HSP) are induced after different stress situations. Some of these proteins, particularly HSP-27, function as markers to indicate cellular stress or damage and protect the heart during addictive processes. Morphine withdrawal induces an enhancement of sympathetic activity in parallel with an increased HSP-27 expression and phosphorylation, indicating a severe situation of stress. HSP-27 can interact with different intracellular signaling pathways. Propranolol and SL-327 were able to antagonize the activation of hypothalamic-pituitary adrenal (HPA) axis and the phosphorylation of HSP-27 observed during morphine withdrawal.  Therefore, β-adrenergic receptors and the extracellular signal-regulated kinase (ERK) pathway would be involved in HPA axis activity, and consequently, in HSP-27 activation. Finally, selective blockade of corticotrophin releasing factor (CRF)-1 receptor and the genetic deletion of CRF1 receptors antagonize cardiac adaptive changes. These changes are increased NA turnover, HPA axis activation and decreased HSP-27 expression and phosphorylation. This suggests a link between HPA axis and HSP-27. On the other hand, morphine withdrawal increases µ-calpain expression, which in turn degrades cardiac troponin T (cTnT). This fact, together with a co-localization between cTnT and HSP-27, suggests that this chaperone avoids the degradation of cTnT by µ-calpain, correcting the cardiac contractility abnormalities observed during addictive processes. The aim of our research is to review the possible role of HSP-27 in the cardiac changes observed during morphine withdrawal and to understand the mechanisms implicated in its cardiac protective functions.
  • 785
  • 02 Nov 2020
Topic Review
Hippo Signaling in Fibrotic Diseases
Fibrosis results from defective wound healing processes often seen after chronic injury and/or inflammation in a range of organs. Progressive fibrotic events may lead to permanent organ damage/failure. The hallmark of fibrosis is the excessive accumulation of extracellular matrix (ECM), mostly produced by pathological myofibroblasts and myofibroblast-like cells. The Hippo signaling pathway is an evolutionarily conserved kinase cascade, which has been described well for its crucial role in cell proliferation, apoptosis, cell fate decisions, and stem cell self-renewal during development, homeostasis, and tissue regeneration.
  • 785
  • 14 Jul 2022
Topic Review
Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization
Hsp90 is a ubiquitous molecular chaperone involved in many cell signaling pathways, and its interactions with specific chaperones and cochaperones determines which client proteins to fold. Hsp90 has been shown to be involved in the promotion and maintenance of proper protein complex assembly either alone or in association with other chaperones such as the R2TP chaperone complex. Hsp90-R2TP acts through several mechanisms, such as by controlling the transcription of protein complex subunits, stabilizing protein subcomplexes before their incorporation into the entire complex, and by recruiting adaptors that facilitate complex assembly.
  • 785
  • 05 Aug 2022
Topic Review
The Receptor Tyrosine Kinase AXL
AXL is a member of the TAM family of receptor tyrosine kinases (RTKs) that also includes TYRO3 and MER. This was the last family of RTKs to be identified and because their inactivation in mice resulted in rather mild phenotypes, their biological roles were slow to be characterized. 
  • 784
  • 18 Apr 2022
Topic Review
L-Lactate Transport in Mitochondria
The L-lactate (L-LAC)-mitochondria affair has its closure: that mitochondria can take up and metabolize L-LAC due to the presence of the mitochondrial L-lactate dehydrogenase is shown.
  • 783
  • 08 Dec 2021
Topic Review
Deubiquitinating Enzyme in HNSCC
Ubiquitin is a highly-conserved small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Ubiquitin was first identified in 1975. It performs its myriad functions through conjugation to a large range of target proteins. A variety of different modifications can occur. This discovery that ubiquitin can be attached to proteins and label them for destruction won the Nobel Prize for chemistry in 2004. The ubiquitin protein consists of 76 amino acids and has a molecular mass of about 8.5 kDa. Under the conditions where ATP provides energy, ubiquitin molecules bind to the target protein through the cascade catalytic reaction of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3). The ubiquitinated target protein is recognized and degraded by 26S proteasome. Ubiquitination and deubiquitination are two popular ways for the post-translational modification of proteins. These two modifications affect intracellular localization, stability, and function of target proteins. The process of deubiquitination is involved in histone modification, cell cycle regulation, cell differentiation, apoptosis, endocytosis, autophagy, and DNA repair after damage. It is involved in the processes of carcinogenesis and cancer development. The deubiquitinating enzyme (DUB) function in head and neck squamous cell carcinoma (HNSCC) is discussed. 
  • 783
  • 12 Jan 2023
Topic Review
Circadian Oscillations in Skin
The term circadian rhythm, defined by Franz Halberg, a pioneer of chronobiology, in 1959, was originally adapted from Greek. It is a hybrid of the words “circa” and “day”, meaning approximately 24 h or a day. In his later work, Halberg described biological cycles, which are an overlay of oscillations that occur in mammals. Circadian rhythm is closely linked to immunological processes and skin homeostasis, and its desynchrony can be linked to the perturbation of the skin. The interplay between circadian rhythm and annual, seasonal oscillations, as well as the impact of these periodic events on the skin, is described.
  • 783
  • 31 Mar 2023
Topic Review
Proto-Oncogene ETS-Related Gene in Prostate Cancer
The ETS-related gene (ERG) is proto-oncogene that is classified as a member of the ETS transcription factor family, which has been found to be consistently overexpressed in about half of the patients with clinically significant prostate cancer (PCa). The overexpression of ERG can mostly be attributed to the fusion of the ERG and transmembrane serine protease 2 (TMPRSS2) genes, and this fusion is represented about 85% of all gene fusions observed in prostate cancer. Clinically, individuals with ERG gene fusion are mostly documented to have advanced tumor stages, increased mortality, and higher rates of metastasis in non-surgical cohorts.
  • 782
  • 13 May 2022
Topic Review
Redox Homeostasis Regulation in Retinal Pigment Epithelium Cells
The retinal pigment epithelium (RPE) performs a range of necessary functions within the neural layers of the retina and helps ensure vision. The regulation of pro-oxidative and antioxidant processes is the basis for maintaining RPE homeostasis and preventing retinal degenerative processes. Long-term stable changes in the redox balance under the influence of endogenous or exogenous factors can lead to oxidative stress (OS) and the development of a number of retinal pathologies associated with RPE dysfunction, and can eventually lead to vision loss. Reparative autophagy, ubiquitin–proteasome utilization, the repair of damaged proteins, and the maintenance of their conformational structure are important interrelated mechanisms of the endogenous defense system that protects against oxidative damage. Antioxidant protection of RPE cells is realized as a result of the activity of specific transcription factors, a large group of enzymes, chaperone proteins, etc., which form many signaling pathways in the RPE and the retina.
  • 782
  • 04 Aug 2023
Topic Review
Roles of the miRISC's Components in Chromatin Biology
The Argonaute (AGO) and the Trinucleotide Repeat Containing 6 (TNRC6) family proteins are the core components of the mammalian microRNA-induced silencing complex (miRISC), the machinery that mediates microRNA function in the cytoplasm. The cytoplasmic miRISC-mediated post-transcriptional gene repression has been established as the canonical mechanism through which AGO and TNRC6 proteins operate. However, growing evidence points towards an additional mechanism through which AGO and TNRC6 regulate gene expression in the nucleus.
  • 781
  • 07 Apr 2022
Topic Review
SLU7 in Human Disease
SLU7 (Splicing factor synergistic lethal with U5 snRNA 7) was first identified as a splicing factor necessary for the correct selection of 3′ splice sites, strongly impacting on the diversity of gene transcripts in a cell. More recent studies have uncovered new and non-redundant roles of SLU7 as an integrative hub of different levels of gene expression regulation, including epigenetic DNA remodeling, modulation of transcription and protein stability.
  • 781
  • 16 Nov 2022
Topic Review
Metabolic Alterations of Diffuse Large B-Cell Lymphoma Macroenvironment
Diffuse large B-cell lymphoma (DLBCL) is aggressive, highly heterogeneous, and the most common form of B-cell lymphoma. Based on cell-of-origin algorithm category and oncogenic mechanisms, DLBCL is classified into three subsets: germinal center B cell-like, activated B cell-like, and unclassifiable subtype. Tumor cells have made some metabolic changes to protect themselves from malnutrition. These metabolic alterations affect the tumor microenvironment and macroenvironment.
  • 781
  • 20 Jun 2023
Topic Review
Molecular Mediators of RNA Loading into Extracellular Vesicles
Extracellular vesicles (EVs) are a family of membrane-coated vesicles with different proteomic and lipidomic profile, as well as different size. An increasing number of studies have demonstrated that non-coding RNA (ncRNAs) cooperate in the gene regulatory networks with other biomolecules, including coding RNAs, DNAs and proteins. Among them, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in transcriptional and translation regulation at different levels. Intriguingly, ncRNAs can be packed in vesicles, released in the extracellular space, and finally internalized by receiving cells, thus affecting gene expression also at distance. 
  • 780
  • 15 Dec 2021
Topic Review
Ocular and Oral Microbiome
The immune-privileged healthy eye has a small unique population of microbiota. Typically, ocular microflorae are commensals of low diversity that colonize the external and internal sites of the eye, without instigating any disorders. Any alteration in the symbiotic relationship culminates in the perturbation of ocular homeostasis and shifts the equilibrium toward local or systemic inflammation and, in turn, impaired visual function. A compositional variation in the ocular microbiota is associated with surface disorders such as keratitis, blepharitis, and conjunctivitis, however, studies now implicate non-ocular microbial dysbiosis in glaucoma, age-related macular degeneration (AMD), uveitis, and diabetic retinopathy. A methodical understanding of the mechanisms of invasion and host-microbial interaction is of paramount importance for preventative and therapeutic interventions for vision-threatening conditions.
  • 779
  • 21 Jun 2022
Topic Review
Fibroblast Growth Factors in the Axon Guidance
Fibroblast growth factors (FGFs), a broad family of polypeptide growth factors, were originally isolated and purified from the pituitary gland of bovines. FGF and FGF receptor (FGFR) signaling pathways play important roles in axon guidance as axons navigate toward their synaptic targets.
  • 779
  • 25 Jun 2023
Topic Review
T-Cell Intracellular Antigen 1
T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein that is expressed in many tissues and in the vast majority of species, although it was first discovered as a component of human cytotoxic T lymphocytes. TIA1 has a dual localization in the nucleus and cytoplasm, where it plays an important role as a regulator of gene-expression flux. As a multifunctional master modulator, TIA1 controls biological processes relevant to the physiological functioning of the organism and the development and/or progression of several human pathologies. 
  • 778
  • 10 Mar 2022
Topic Review
Wnt Signaling Pathway in Liver Metastasis
Liver metastasis, originating either from a primary liver or other cancer types, represent a large cancer-related burden. Therefore, studies that add to better understanding of its molecular basis are needed. Herein, the role of the Wnt signaling pathway in liver metastasis is outlined. Its role in hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT), motility, migration, metastasis formation, and other steps of the metastatic cascade are presented. Additionally, the roles of the Wnt signaling pathway in the liver metastasis formation of colorectal, breast, gastric, lung, melanoma, pancreatic, and prostate cancer are explored.
  • 777
  • 03 Nov 2021
Topic Review
MiRNA Detection and Biosensing
MicroRNAs (miRNA) are key regulators of gene expression, controlling different biological processes such as cellular development, differentiation, proliferation, metabolism, and apoptosis. The relationships between miRNA expression and the onset and progression of different diseases, such as tumours, cardiovascular and rheumatic diseases, and neurological disorders, are well known. A nanotechnology-based approach could match miRNA delivery and detection to move beyond the proof-of-concept stage. Different kinds of nanotechnologies can have a major impact on the diagnosis and treatment of miRNA-related diseases such as cancer. 
  • 777
  • 01 Jul 2022
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