Endosomal sorting complex required for transport (ESCRT) system drives various cellular processes, including endosome sorting, organelle biogenesis, vesicle transport, maintenance of plasma membrane integrity, membrane fission during cytokinesis, nuclear membrane reformation after mitosis, closure of autophagic vacuoles, and enveloped virus budding. Increasing evidence suggests that the ESCRT system can be hijacked by different family viruses for their proliferation. At different stages of the virus life cycle, viruses can interfere with or exploit ESCRT-mediated physiological processes in various ways to maximize their chance of infecting the host. In addition, many retroviral and RNA viral proteins possess \"late domain\" motifs, which can recruit host ESCRT subunit proteins to assist in virus endocytosis, transport, replicate, budding and efflux. Therefore, the \"late domain\" motifs of viruses and ESCRT subunit proteins could serve as promising drug targets in antiviral therapy. This review focuses on the composition and functions of the ESCRT system, the effects of ESCRT subunits and virus \"late domain\" motifs on viral replication, and the antiviral effects mediated by the ESCRT system, aiming to provide a reference for the development and utilization of antiviral drugs.

The discovery of the insulin hormone over 100 years ago, and its subsequent therapeutic application, marked a key landmark in the history of medicine and medical research. The many roles insulin plays in cell metabolism and growth have been revealed by extensive investigations into the structure and function of insulin, the insulin tyrosine kinase receptor (IR), as well as the signalling cascades, which occur upon insulin binding to the IR. In this review, the insulin gene mutations identified as causing disease and the structural implications of these mutations will be discussed. Over 100 studies were evaluated by one reviewing author, and over 70 insulin gene mutations were identified. Mutations may impair insulin gene transcription and translation, preproinsulin trafficking and proinsulin sorting, or insulin-IR interactions. A better understanding of insulin gene mutations and the resultant pathophysiology can give essential insight into the molecular mechanisms underlying impaired insulin biosynthesis and insulin-IR interaction.

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by pathogenic variants of the vacuolar protein sorting 13A (VPS13A). Only a few patients with ChAc have been reported to date, and the variant spectrum of VPS13A has not been completely elucidated. We describe the case of a 36-year-old woman who had been experiencing orofacial dyskinesia since age 30 years. In a genetic study using next-generation sequencing, 2 variants of VPS13A, the nonsense variant c.4411C>T (p.Arg1471Ter) and the splicing variant c.145-2A>T, were identified. The splicing variant c.145-2A>T was newly classified as a pathogenic variant through a literature review. Consequently, the patient was diagnosed with ChAc based on the typical clinical manifestations, laboratory findings, and imaging results.

Soybean is one of the most important sources of plant protein and is known for its wide range of agricultural, food, and industrial applications as well as health benefits. Interest in soybean proteins has been steadily growing as progressively more applications and benefits are discovered. This review article is focused on the major seed storage proteins of soybean, their three-dimensional structures, their nutritional importance and bioactive peptides, cellular synthesis, and accumulation in seeds. This will also summarize past efforts in the recombinant production of foreign proteins or bioactive peptides in soybean seed.

The translocases of the mitochondrial outer and inner membranes, the TOM and TIMs, import hundreds of nucleus-encoded proteins into mitochondria. TOM and TIMs are multi-subunit protein complexes that work in cooperation with other complexes to import proteins in different sub-mitochondrial destinations. The overall architecture of these protein complexes is conserved among yeast/fungi, animals, and plants. Recent studies have revealed unique characteristics of this machinery, particularly in the eukaryotic supergroup Excavata. Despite multiple differences, homologues of Tim17, an essential component of one of the TIM complexes and a member of the Tim17/Tim22/Tim23 family, have been found in all eukaryotes. Here, we review the structure and function of Tim17 and Tim17-containing protein complexes in different eukaryotes, and then compare them to the single homologue of this protein found in Trypanosoma brucei, a unicellular parasitic protozoan.

Intraflagellar transport (IFT) is an essential process in all organisms that serves to move proteins along flagella or cilia in either direction. IFT is performed by IFT particles, which are multiprotein complexes organized into two subcomplexes, A and B. The IFT proteins form interactions with each other, with cargo proteins, and with membranes during the transport process. Several IFT proteins are expressed in many parts of the retina, such as the outer plexiform and outer nuclear layers, and function in the transport of photoreceptor proteins between the inner and outer segments. Mutants of IFT protein genes have been characterized in model organisms such as Chlamydomonas, C. elegans, zebrafish, and the mouse. These mutants have defective ciliogenesis or abnormalities in retinal photoreceptors. Mutations in IFT genes are associated with syndromic and non-syndromic forms of retinal disease in humans, frequently with early onset of disease.

The process of autophagy is integral to cellular function. In this process, proteins, organelles, and metabolites are engulfed in a lipid vesicle and trafficked to a lysosome for degradation. Its central role in protein and organelle homeostasis has piqued interest for autophagy dysfunction as a driver of pathology for a number of diseases including cancer, muscular disorders, neurological disorders, and non-alcoholic fatty liver disease. For much of its history, the study of autophagy has centered around proteins, however, due to advances in mass spectrometry and refined methodologies, the role of lipids in this essential cellular process has become more apparent. This review discusses the diverse endogenous lipid compounds shown to mediate autophagy. Downstream lipid signaling pathways are also reviewed in the context of autophagy regulation. Specific focus is placed upon the Mammalian Target of Rapamycin (mTOR) and Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathways as integration hubs for lipid regulation of autophagy.

Nephrogenic diabetes insipidus (NDI) is characterized by renal resistance to the antidiuretic hormone arginine vasopressin (AVP), which leads to polyuria, plasma hyperosmolarity, polydipsia, and impaired quality of living. Inherited forms are caused by X-linked loss-of-function mutations in the gene encoding the vasopressin 2 receptor (V2R) or autosomal recessive/dominant mutations in the gene encoding aquaporin 2 (AQP2). A common acquired form is lithium-induced NDI. AVP facilitates reabsorption of water through increased abundance and insertion of AQP2 in the apical membrane of principal cells in the collecting ducts. In X-linked NDI, V2R is dysfunctional, which leads to impaired water reabsorption. These patients have functional AQP2, and thus the challenge is to achieve AQP2 membrane insertion independently of V2R. The current treatment is symptomatic and is based on distally acting diuretics (thiazide or amiloride) and cyclooxygenase inhibitors (indomethacin). This mini-review covers published data from trials in preclinical in vivo models and a few human intervention studies to improve NDI by more causal approaches. Promising effects on NDI in preclinical studies have been demonstrated by the use of pharmacological approaches with secretin, Wnt5a, protein kinase A agonist, fluconazole, prostaglandin E2 EP2 and EP4 agonists, statins, metformin, and soluble prorenin receptor agonists. In patients, only casuistic reports have evaluated the effect of statins, phosphodiesterase inhibitors (rolipram and sildenafil), and the guanylate cyclase stimulator riociguat without amelioration of symptoms. It is concluded that there is currently no established intervention that causally improves symptoms or quality of life in patients with NDI. There is a need to collaborate to improve study quality and conduct formal trials.

In recent years, large amounts of peptides have been purified and characterized from food protein hydrolysates. Many of these peptides have been demonstrated to be of potential application as health-improving ingredients against plenty of disease conditions, such as cancer, inflammation, and cardiovascular disease. The real efficacy of functional application of these peptides depends on their stability, transport, and bioavailability in target tissues, which in turn depends on the peptides characteristics. Therefore, the characteristic-function parameters are crucial for peptides using as functional agents. This review article intends to summarize the effects of peptide characteristics, including molecular weight, charge and hydrophobicity, on their stability, intestinal transport, and in vitro bioavailability. PRACTICAL APPLICATIONS: In the near future, bioactive peptides will play important roles in the area of functional foods and pharmacy. However, the gastrointestinal digestion and transport usually restrict their bioavailability in vivo. Understanding the relationships between peptide characteristics and their digestion stability, bioavailability may provide guidance and theoretical basis for the further application of bioactive peptides.

FAK is a tyrosine kinase overexpressed in cancer cells and plays an important role in the progression of tumors to a malignant phenotype. Except for its typical role as a cytoplasmic kinase downstream of integrin and growth factor receptor signaling, related studies have shown new aspects of the roles of FAK in the nucleus. FAK can promote p53 degradation through ubiquitination, leading to cancer cell growth and proliferation. FAK can also regulate GATA4 and IL-33 expression, resulting in reduced inflammatory responses and immune escape. These findings establish a new model of FAK from the cytoplasm to the nucleus. Activated FAK binds to transcription factors and regulates gene expression. Inactive FAK synergizes with different E3 ligases to promote the turnover of transcription factors by enhancing ubiquitination. In the tumor microenvironment, nuclear FAK can regulate the formation of new blood vessels, affecting the tumor blood supply. This article reviews the roles of nuclear FAK in regulating gene expression. In addition, the use of FAK inhibitors to target nuclear FAK functions will also be emphasized.