Protein degradation

PA28γ is a proteasomal interactor whose main and most known function is to stimulate the hydrolytic activity of the 20S proteasome independently of ubiquitin and ATP. Unlike its two paralogues, PA28α and PA28β, PA28γ is largely present in the nuclear compartment and plays pivotal functions in important pathways such as cellular division, apoptosis, neoplastic transformation, chromatin structure and organization, fertility, lipid metabolism, and DNA repair mechanisms. Although it is known that a substantial fraction of PA28γ is found in the cell in a free form (i...

Tuberculosis (TB) is a serious cause of infectious death worldwide. Recent studies have reported that about 30% of the Mtb proteome was modified post-translationally, indicating that their functions are essential for drug resistance, mycobacterial survival, and pathogenicity. Among them, lysine acetylation, reversibly regulated by acetyltransferase and deacetylase, has important roles involved in energy metabolism, cellular adaptation, and protein interactions. However, the substrate and biological functions of these two important regulatory enzymes remain unclear...

To enhance market demand and fish utilization, cutting processing is essential for fish. Bighead carp were cut into four primary cuts: head, dorsal, belly, and tail, collectively accounting for 77.03% of the fish's total weight. These cuts were refrigerated at 4 °C for 10 days, during which the muscle from each cut was analyzed. Pseudomonas.fragi proliferated most rapidly and was most abundant in eye muscle (EM), while Aeromonas.sobria showed similar growth patterns in tail muscle (TM). Notably, EM exhibited the highest rate of fat oxidation...

The organic matter (OM) and nitrogen in Fresh leachate (FL) from waste compression sites pose environmental and health risks. Even though the constructed wetland (CW) can efficiently remove these pollutants, the molecular-level transformations of dissolved OM (DOM) in FL remain uncertain. This study reports the molecular dynamics of DOM and nitrogen removal during FL treatment in CWs. Two lab-scale vertical-flow CW systems were employed: one using only sand as substrates (act as a control, CW-C) and the other employing an equal mixture of manganese ore powder and sand (experimental, CW-M)...

Non-ionic surfactants such as Polysorbate 20/ 80 (PS20/ PS80), are commonly used in protein drug formulations to increase protein stability by protecting against interfacial stress and surface absorption. Polysorbate is susceptible to degradation which can impact product stability, leading to the formation of sub-visible and/or visible particles in the drug product during its shelf-life, affecting patient safety and efficacy. Therefore, it is important to monitor polysorbate concentration in drug product formulations of biotherapeutic drugs...

The sea cucumber plasmalogen PlsEtn has been shown to be associated with various chronic diseases related to lipid metabolism. However, the mechanism is unclear. Therefore, the present study used the sea cucumber plasmanylcholine PakCho as a structural contrast to PlsEtn and assessed its effect in 8 week high-fat diet (HFD)-fed mice. The lipidomic approach based on high-resolution mass spectrometry combined with molecular biology techniques was used to evaluate the mechanism of PlsEtn. The results showed that both PlsEtn and PakCho significantly inhibited an increase in mouse body weight and liver total triglyceride and total cholesterol levels caused by HFD...

This chapter aims to provide a comprehensive overview of the methodologies available to dissect genetic regulation of the nervous systems in the nematode Caenorhabditis elegans. These techniques encompass genetic screens and genetic tools to unravel the spatial-temporal contribution of genes on neural structure and function. Unbiased genetic screens on random mutations induced by ethyl methanesulfonate (EMS) or target gene silencing by genome-wide RNA interference (RNAi) help progress our understanding of the genetic control of neural development and functions...

The exploitation of exciting features of plastics for diverse applications has resulted in significant plastic waste generation, which negatively impacts environmental compartments, metabolic processes, and the well-being of aquatic ecosystems biota. A shotgun metagenomic approach was deployed to investigate the microbial consortia, degradation pathways, and enzyme systems involved in the degradation of plastics in a tropical lentic pond sediment (APS). Functional annotation of the APS proteome (ORFs) using the PlasticDB database revealed annotation of 1015 proteins of enzymes such as depolymerase, esterase, lipase, hydrolase, nitrobenzylesterase, chitinase, carboxylesterase, polyesterase, oxidoreductase, polyamidase, PETase, MHETase, laccase, alkane monooxygenase, among others involved in the depolymerization of the plastic polymers...

De novo acute myeloid leukemia (AML) patients with FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD) have worse treatment outcomes. Arsenic trioxide (ATO) used in the treatment of acute promyelocytic leukemia (APL) has been reported to be effective in degrading the FLT3 protein in AML cell lines and sensitizing non-APL AML patient samples in-vitro. We have previously reported that primary cells from FLT3-ITD mutated AML patients were sensitive to ATO in-vitro compared to other non-M3 AML and molecular/pharmacological inhibition of NF-E2 related factor 2 (NRF2), a master regulator of antioxidant response improved the chemosensitivity to ATO and daunorubicin even in non FLT3-ITD mutated cell lines and primary samples...

Ubiquitination-mediated protein degradation is integral to plant immunity, with E3 ubiquitin ligases acting as key factors in this process. Here, we report the functions of OsATL32, a plasma membrane-localized Arabidopsis Tóxicos En Levadura (ATL)-type E3 ubiquitin ligase, in rice (Oryza sativa) immunity and its associated regulatory network. We found that the expression of OsATL32 is downregulated in both compatible and incompatible interactions between rice and the rice blast fungus Magnaporthe oryzae...

The preservation of genome integrity requires specialised DNA damage repair (DDR) signalling pathways to respond to each type of DNA damage. A key feature of DDR is the integration of numerous post-translational modification signals with DNA repair factors. These modifications influence DDR factor recruitment to damaged DNA, activity, protein-protein interactions, and ultimately eviction to enable access for subsequent repair factors or termination of DDR signalling. SUMO1-3 (small ubiquitin-like modifier 1-3) conjugation has gained much recent attention...

The RNA modification N6-methyladenosine (m6A) is conserved across eukaryotes, and profoundly influences RNA metabolism, including regulating RNA stability. METTL3 and METTL14, together with several accessory components, form a 'writer' complex catalysing m6A modification. Conversely, FTO and ALKBH5 function as demethylases, rendering m6A dynamic. Key to understanding the functional significance of m6A is its 'reader' proteins, exemplified by YTH-domain-containing proteins (YTHDFs) canonical reader and insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) non-canonical reader...

DOM is the largest reservoir of organic carbon in the world, and it plays a crucial role in the biogeochemical cycles of natural water bodies. A river is a transition area connecting source water and receiving water that controls the DOM exchange between them. Therefore, in this study, ultraviolet visible spectroscopy (UV-vis) and three-dimensional fluorescence spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC) were used to analyze the spectral characteristics and sources of dissolved organic matter in the Fuhe River, Xiaobai River, Baigouyin River, and Puhe River of Baiyangdian...

Seminal roots play a critical role in water and nutrient absorption, particularly in the early developmental stages of wheat. However, the genes responsible for controlling SRN in wheat remain largely unknown. Genetic mapping and functional analyses identified a candidate gene (TraesCS3D01G137200, TaSRN-3D) encoding a Ser/Thr kinase glycogen synthase kinase 3 (STKc_GSK3) that regulated SRN in wheat. Additionally, experiments involving hormone treatment, nitrate absorption and protein interaction were conducted to explore the regulatory mechanism of TaSRN-3D...

Thioredoxin domain containing protein-5 (TXNDC5), also known as endothelial protein-disulfide isomerase (Endo-PDI), is confined to the endoplasmic reticulum through the structural endoplasmic reticulum retention signal (KDEL), is a member of the PDI protein family and is highly expressed in the hypoxic state. TXNDC5 can regulate the rate of disulfide bond formation, isomerization and degradation of target proteins through its function as a protein disulfide isomerase (PDI), thereby altering protein conformation, activity and improving protein stability...

Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase...

Cold-adapted proteases are capable of efficient protein hydrolysis at reduced temperatures, which offer significant potential applications in the area of low temperature food processing. In this paper, we attempted to characterize cold-adapted proteases from Antarctic krill. Antarctic krill possesses an extremely active autolytic enzyme system in their bodies, and the production of peptides and free amino acids accompanies the rapid breakdown of muscle proteins following the death. The crucial role of trypsin in this process is recognized...

BACKGROUND: Anuran metamorphosis, which is driven by thyroid hormone (TH)-mediated processes, orchestrates intricate morphological and functional transformations for the transition from aquatic tadpoles to terrestrial life, providing a valuable model for studying organ functionalization, remodeling, and regression. Larva-specific organ regression is one of the most striking phenomena observed during the anuran metamorphic climax. While previous studies extensively analyzed the regression mechanisms of the tail, the molecular processes governing gill resorption remain elusive...

BACKGROUND: To explore the safety of Neodymium:Yttrium-aluminum-garnet (Nd:YAG) laser vitreolysis based on the histological examination of the retina and the alteration of vitreous cytokines in the rabbits. METHODS: Nine male New Zealand rabbits underwent Nd:YAG laser vitreolysis of 10 mJ x 500 pulses in the left eyes, while the right eyes were used as controls. Intraocular pressure, color fundus photography, and ultrasound B scan were measured before, as well as 1 day, 4 weeks, and 12 weeks after Nd:YAG laser vitreolysis...

The hypomethylating agent 5-azacytidine (AZA) is the first-line treatment for AML patients unfit for intensive chemotherapy. The effect of AZA results in part from T-cell cytotoxic responses against MHC-I-associated peptides (MAPs) deriving from hypermethylated genomic regions such as cancer-testis antigens (CTAs), or endogenous retroelements (EREs). However, evidence supporting higher ERE MAPs presentation after AZA treatment is lacking. Therefore, using proteogenomics, we examined the impact of AZA on the repertoire of MAPs and their source transcripts...