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Topic Review
Maturation of Mitochondrial [4Fe-4S]-Containing Proteins
The importance of mitochondria in mammalian cells is widely known. Several biochemical reactions and pathways take place within mitochondria: among them, there are those involving the biogenesis of the iron–sulfur (Fe-S) clusters. The latter are evolutionarily conserved, ubiquitous inorganic cofactors, performing a variety of functions, such as electron transport, enzymatic catalysis, DNA maintenance, and gene expression regulation. The synthesis and distribution of Fe-S clusters are strictly controlled cellular processes that involve several mitochondrial proteins that specifically interact each other to form a complex machinery (Iron Sulfur Cluster assembly machinery, ISC machinery hereafter). This machinery ensures the correct assembly of both [2Fe-2S] and [4Fe-4S] clusters and their insertion in the mitochondrial target proteins. 
  • 967
  • 02 Aug 2022
Topic Review
Receptor-Arrestin Interactions
Arrestins are a small family of four proteins in most vertebrates that bind hundreds of different G protein-coupled receptors (GPCRs). Arrestin binding to a GPCR has at least three functions: precluding further receptor coupling to G proteins, facilitating receptor internalization, and initiating distinct arrestin-mediated signaling. The molecular mechanism of arrestin–GPCR interactions has been extensively studied and discussed from the “arrestin perspective”, focusing on the roles of arrestin elements in receptor binding.
  • 966
  • 19 Feb 2021
Topic Review
Tibolone
Low bone mineral density (osteoporosis) is associated with vertebral and nonvertebral fractures in postmenopausal women. Tibolone is a low-risk hormone replacement therapy alternative to estrogen therapy, effective in the treatment of menopausal symptoms and prevention of bone loss, but the evidence is controversial. This study with meta-analysis summarizes the clinical trials of the tibolone effect on percentage change of bone mineral density in the lumbar spine, femoral neck, and total hip in postmenopausal women.
  • 966
  • 01 Apr 2021
Topic Review
Peptide Binding at Class A G Protein-Coupled Receptors
G protein-coupled receptors (GPCRs) represent the largest membrane protein family and a significant target class for therapeutics. Receptors from GPCRs’ largest class, class A, influence virtually every aspect of human physiology. About 45% of the members of this family endogenously bind flexible peptides or peptides segments within larger protein ligands. While many of these peptides have been structurally characterized in their solution state, the few studies of peptides in their receptor-bound state suggest that these peptides interact with a shared set of residues and undergo significant conformational changes. 
  • 966
  • 06 Jan 2022
Topic Review
DNA-Dependent Protein Kinase in Non-Homologous End Joining
DNA-dependent protein kinase (DNA-PK), which is composed of a DNA-PK catalytic subunit (DNA-PKcs) and Ku80-Ku70 heterodimer, acts as the molecular sensor for DSB and plays a pivotal role in DSB repair through non-homologous end joining (NHEJ). Cells deficient for DNA-PKcs show hypersensitivity to IR and several DNA-damaging agents. Cellular sensitivity to IR and DNA-damaging agents can be augmented by the inhibition of DNA-PK. A number of small molecules that inhibit DNA-PK have been developed. 
  • 966
  • 05 May 2022
Topic Review
CMGC Kinases in Health and Cancer
CMGC kinases, encompassing cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAPKs), glycogen synthase kinases (GSKs), and CDC-like kinases (CLKs), play pivotal roles in cellular signaling pathways, including cell cycle regulation, proliferation, differentiation, apoptosis, and gene expression regulation. The dysregulation and aberrant activation of these kinases have been implicated in cancer development and progression, making them attractive therapeutic targets. Kinase inhibitors targeting CMGC kinases, such as CDK4/6 inhibitors and BRAF/MEK inhibitors, have demonstrated clinical success in treating specific cancer types.
  • 966
  • 01 Aug 2023
Topic Review
PGC-1s in Parkinson’s Disease
The family of peroxisome proliferator-activated receptor γ coactivator 1 comprises three members, PGC-1α, PGC-1β, and PGC-related coactivator (PRC). PGC-1s act as ‘molecular switches’ in many metabolic pathways, coordinating transcriptional programs involved in the control of cellular metabolism and overall energy homeostasis as well as antioxidant defence.
  • 965
  • 28 Apr 2021
Topic Review
Development of Phosphodiesterase–Protein-Kinase Complexes
Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to modulate multiple signaling events in cells. PDEs are recognized to actively associate with cyclic nucleotide receptors (protein kinases, PKs) in larger macromolecular assemblies referred to as signalosomes. Complexation of PDEs with PKs generates an expanded active site that enhances PDE activity. This facilitates signalosome-associated PDEs to preferentially catalyze active hydrolysis of cyclic nucleotides bound to PKs and aid in signal termination. PDEs are important drug targets, and current strategies for inhibitor discovery are based entirely on targeting conserved PDE catalytic domains. This often results in inhibitors with cross-reactivity amongst closely related PDEs and attendant unwanted side effects. 
  • 965
  • 22 Jun 2021
Topic Review
LncRNAs in Translation
Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Depending on cellular location, lncRNAs are involved in a wide range of cellular functions, including chromatin modification, transcriptional activation, transcriptional interference, scaffolding and regulation of translational machinery.
  • 964
  • 19 Apr 2021
Topic Review
Endomembrane System and Abiotic Stress in Plants
The sustainable exploitation of agri-environmental systems focuses more and more on practices where crops and plant species are adapted to edaphoclimatic conditions. Recent studies have shown that increased stress tolerance is related to the reorganization of cell membranes that sometimes lead to major changes in the solutes’ homeostasis and water transfer. When under stress, protein trafficking in plants is compromised, usually leading to changes in the endomembrane system that may include protein transport through unconventional routes and alteration of morphology, activity and content of key organelles, as the ER and the vacuole. Such events provide the tools for cells to adapt and overcome the challenges brought on by stress.
  • 964
  • 18 Feb 2022
Topic Review
Implications of One-Carbon and Polyamine Metabolism for Cancer
Cancer metabolic reprogramming is essential for maintaining cancer cell survival and rapid replication. A common target of this metabolic reprogramming is one-carbon metabolism which is notable for its function in DNA synthesis, protein and DNA methylation, and antioxidant production. Polyamines are a key output of one-carbon metabolism with widespread effects on gene expression and signaling. One-carbon metabolism includes the methionine cycle, which is linked to the folate cycle, polyamine synthesis, and the trans-sulphuration pathway. 
  • 963
  • 17 Jan 2023
Topic Review
Bulk purification of RNA–Protein Complexes
The ribonome interconnects the proteome and the transcriptome. Specific biology is situated at this interface, which can be studied in bulk using omics approaches. In this entry, we focus on both RNA- and ribonucleoprotein-(RNP) centric methods. These methods can be used to study the dynamics of the ribonome in response to a stimulus. The purpose of this entry is to provide and discuss an overview of the currently available RNA- and RNP-centric approaches to study RNPs. 
  • 962
  • 19 Aug 2020
Topic Review
Mitochondrial Diseases
Mitochondrial DNA (mtDNA) diseases are a group of maternally inherited genetic disorders caused by a lack of energy production.
  • 962
  • 04 Feb 2021
Topic Review
Mammalian Unfolded Protein Response Transducers
The unfolded protein response (UPR) bears an evolutionary conserved, dual sensitivity to both protein-folding imbalances in the endoplasmic reticulum (ER) lumen and aberrant compositions of the ER membrane, referred to as lipid bilayer stress (LBS). Through transcriptional and non-transcriptional mechanisms, the UPR upregulates the protein folding capacity of the ER and balances the production of proteins and lipids to maintain a functional secretory pathway.
  • 961
  • 03 Nov 2021
Topic Review
Plant Toxins: Recombinant Production as Components of Immunotoxins
Plant toxins that target eukaryotic 28S ribosomal RNA (Ribosome Inactivating Proteins, RIPs), such as the catalytic (A) chain of ricin (a dimeric A-B toxin from Ricinus communis) and saporin (a single chain A toxin from Saponaria officinalis), have found widespread use in the construction of immunotoxins. Both these toxins depurinate ribosomal 28S RNA at a specific site (GAGA loop) inhibiting the binding of elongation factor 2 and blocking protein synthesis. Their high toxicity towards eukaryotic cells has thus justified their use as components of chimeric toxins in cancer treatment. A brief description of recombinant RIPs production is given.
  • 961
  • 02 Jan 2024
Topic Review
Phytochrome-Interacting Proteins
Phytochromes are photoreceptors of plants, fungi, slime molds bacteria and heterokonts. These biliproteins sense red and far-red light and undergo light-induced changes between the two spectral forms, Pr and Pfr. Photoconversion triggered by light induces conformational changes in the bilin chromophore around the ring C-D-connecting methine bridge and is followed by conformational changes in the protein. For plant phytochromes, multiple phytochrome interacting proteins that mediate signal transduction, nuclear translocation or protein degradation have been identified. Few interacting proteins are known as bacterial or fungal phytochromes.
  • 961
  • 10 Jan 2024
Topic Review
GPCR signaling in the carotid-body
       The carotid body (CB) is a vital sensory organ, located near the carotid bifurcation, that constantly monitors blood supplying the brain. The CB is stimulated by acute hypoxia, upon which it rapidly activates vital cardiovascular and respiratory reflexes, including peripheral vasoconstriction, elevated heart rate and increased breathing. These ensure that sufficient blood-oxygen is delivered to the brain to support survival. It is now apparent that there are numerous G-protein-coupled receptors (GPCRs) expressed in the CB, and that modulation of these receptors is able to alter baseline CB activity and the sensitivity to hypoxia. Indeed, components of GPCR signaling pathways represent some of the most highly expressed genes in the rodent CB.
  • 960
  • 25 Aug 2020
Topic Review
Bacterial Pathogens Secretory System Components
Bacterial secretory systems are essential for virulence in human pathogens. The systems have become a target of alternative antibacterial strategies based on small molecules and antibodies. Strategies to use components of the systems to design prophylactics have been less publicized despite vaccines being the preferred solution to dealing with bacterial infections.
  • 960
  • 09 Jul 2021
Topic Review
Breast Cancer Management and Extracellular Vesicle Research
Extracellular vesicles are lipid bilayer-enclosed particles released from all types of cells and found in biological fluids, which transport variable content and have crucial functions in cell–cell communication. The role of extracellular vesicles in cancer is a current hot topic, and no bibliometric study has ever analyzed research production regarding their role in breast cancer and indicated the trends in the field. In this way, the study aimed to investigate the trends in breast cancer management involved with extracellular vesicle research.
  • 960
  • 23 Nov 2021
Topic Review
Autoimmunity and Inflammation of RA
Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease identified by continuous joint inflammation promoting cartilage and bone damage, incapacity, and eventually systemic complications.
  • 959
  • 19 Jan 2021
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