Protein turnover

Here, we show that insulin induces palmitoylation turnover of Caveolin-2 (Cav-2) in adipocytes. Acyl protein thioesterases-1 (APT1) catalyzes Cav-2 depalmitoylation, and zinc finger DHHC domain-containing protein palmitoyltransferase 21 (ZDHHC21) repalmitoylation of the depalmitoylated Cav-2 for the turnover, thereby controlling insulin receptor (IR)-Cav-2-insulin receptor substrate-1 (IRS-1)-Akt-driven signaling. Insulin-induced palmitoylation turnover of Cav-2 facilitated glucose uptake and fat storage through induction of lipogenic genes...

Understanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting nuclear RNA-protein equilibrium...

The microtubule cytoskeleton is responsible for sustained, long-range intracellular transport of mRNAs, proteins, and organelles in neurons. Neuronal microtubules must be stable enough to ensure reliable transport, but they also undergo dynamic instability, as their plus and minus ends continuously switch between growth and shrinking. This process allows for continuous rebuilding of the cytoskeleton and for flexibility in injury settings. Motivated by in vivo experimental data on microtubule behavior in Drosophila neurons, we propose a mathematical model of dendritic microtubule dynamics, with a focus on understanding microtubule length, velocity, and state-duration distributions...

Ubiquitylation regulates most proteins and biological processes in a eukaryotic cell. However, the site-specific occupancy (stoichiometry) and turnover rate of ubiquitylation have not been quantified. Here we present an integrated picture of the global ubiquitylation site occupancy and half-life. Ubiquitylation site occupancy spans over four orders of magnitude, but the median ubiquitylation site occupancy is three orders of magnitude lower than that of phosphorylation. The occupancy, turnover rate, and regulation of sites by proteasome inhibitors are strongly interrelated, and these attributes distinguish sites involved in proteasomal degradation and cellular signaling...

Protein tyrosine nitration (PTN) by oxidative and nitrative stress is a well-known post-translational modification that plays a role in the initiation and progression of various diseases. Despite being recognized as a stable modification for decades, recent studies have suggested the existence of a reduction in PTN, leading to the formation of 3-aminotyrosine (3AT) and potential denitration processes. However, the vital functions of 3AT-containing proteins are still unclear due to the lack of selective probes that directly target the protein tyrosine amination...

Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/CCDH1 ) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/CCDH1 activity to treat cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)-catalyzed phosphorylation-dependent cis-trans prolyl isomerization drives tumor malignancy...

UNLABELLED: Biomolecular condensates, such as the nucleoli or P-bodies, are non-membrane-bound assemblies of proteins and nucleic acids that facilitate specific cellular processes. Like eukaryotic P-bodies, the recently discovered bacterial ribonucleoprotein bodies (BR-bodies) organize the mRNA decay machinery, yet the similarities in molecular and cellular functions across species have been poorly explored. Here, we examine the functions of BR-bodies in the nitrogen-fixing endosymbiont Sinorhizobium meliloti , which colonizes the roots of compatible legume plants...

Receptor-mediated cellular uptake of specific ligands constitutes an important step in the dynamic regulation of individual protein levels in extracellular fluids. With a focus on the inflammatory lung, we here performed a proteomics-based search for novel ligands regulated by the mannose receptor (MR), a macrophage-expressed endocytic receptor. Wildtype and MR-deficient mice were exposed to lipopolysachharide (LPS), after which the protein content in their lung epithelial lining fluid (ELF) was compared by tandem mass tag-based mass spectrometry...

Salt stress significantly impacts the functions of the photosynthetic apparatus, with varying degrees of damage to its components. Photosystem II (PSII) is more sensitive to environmental stresses, including salinity, than photosystem I (PSI). This study investigated the effects of different salinity levels (0 to 200 mM NaCl) on the PSII complex in isolated thylakoid membranes from hydroponically grown pea ( Pisum sativum L.) and maize ( Zea mays L.) plants treated with NaCl for 5 days. The data revealed that salt stress inhibits the photochemical activity of PSII (H2 O → BQ), affecting the energy transfer between the pigment-protein complexes of PSII (as indicated by the fluorescence emission ratio F695 /F685 ), QA reoxidation, and the function of the oxygen-evolving complex (OEC)...

The proteasome is a multisubunit protease system responsible for the majority of the protein turnover in eukaryotic organisms. Dysregulation of this enzymatic complex leads to protein accumulation, subsequent aggregation, and ultimately diseased states; for that reason, positive modulation of its activity has been recently investigated as a therapeutic strategy for neurodegenerative and age-related diseases. The small molecule AM404 was recently identified as an activator of the 20S isoform of the proteasome and further exploration of the scaffold revealed the importance of the polyunsaturated fatty acid chain to elicit activity...

Skeletal muscle mass is critical for activities of daily living. Resistance training maintains or increases muscle mass, and various strategies maximize the training adaptation. Mesenchymal stem cells (MSCs) are multipotent cells with differential potency in skeletal muscle cells and the capacity to secrete growth factors. However, little is known regarding the effect of intramuscular injection of MSCs on basal muscle protein synthesis and catabolic systems after resistance training. Here, we measured changes in basal muscle protein synthesis, the ubiquitin-proteasome system, and autophagy-lysosome system-related factors after bouts of resistance exercise by intramuscular injection of MSCs...

The integrated stress response (ISR) is a key cellular signaling pathway activated by environmental alterations that represses protein synthesis to restore homeostasis. To prevent sustained damage, the ISR is counteracted by the upregulation of growth arrest and DNA damage-inducible 34 (GADD34), a stress-induced regulatory subunit of protein phosphatase 1 that mediates translation reactivation and stress recovery. Here, we uncover a novel ISR regulatory mechanism that post-transcriptionally controls the stability of PPP1R15A mRNA encoding GADD34...

ABSCISIC ACID (ABA) INSENSITIVE5 (ABI5), the key regulator of abscisic acid (ABA) signaling pathway, plays a fundamental role in seed germination and postgerminative development. However, the detailed molecular mechanism underlying the repression function of ABI5 in these processes remains to be elucidated. In this study, we demonstrate that the conserved eukaryotic WD40 repeat protein RACK1 is a novel negative regulator of ABI5 in Arabidopsis. The RACK1 loss-of-function mutant is hypersensitive to ABA, while this phenotype was rescued by the mutation of ABI5...

Proteostasis of the endoplasmic reticulum (ER) is maintained by coordinated action of two major catabolic pathways: proteasome-dependent ER-associated degradation (ERAD) and less characterized lysosomal pathways. Recent studies on ER-specific autophagy (termed "reticulophagy") have highlighted the importance of lysosomes for ER proteostasis. Key to this process are proteins termed reticulophagy receptors that connect ER fragments and Atg8-family proteins, facilitating the lysosomal degradation of both native and aberrant ER proteins in a relatively nonselective manner...

DEAD- and DExH-box ATPases (DDX/DHXs) are abundant and highly conserved cellular enzymes ubiquitously involved in RNA processing. By remodeling RNA-RNA and RNA-protein interactions, they often function as gatekeepers that control the progression of diverse RNA maturation steps. Intriguingly, most DDX/DHXs localize to membraneless organelles (MLOs) such as nucleoli, nuclear speckles, stress granules, or processing bodies. Recent findings suggest not only that localization to MLOs can promote interaction between DDX/DHXs and their targets but also that DDX/DHXs are key regulators of MLO formation and turnover through their condensation and ATPase activity...

RNA isoforms influence cell identity and function. However, a comprehensive brain isoform map was lacking. We analyze single-cell RNA isoforms across brain regions, cell subtypes, developmental time points and species. For 72% of genes, full-length isoform expression varies along one or more axes. Splicing, transcription start and polyadenylation sites vary strongly between cell types, influence protein architecture and associate with disease-linked variation. Additionally, neurotransmitter transport and synapse turnover genes harbor cell-type variability across anatomical regions...

Helicases, motor proteins present in both prokaryotes and eukaryotes, play a direct role in various steps of RNA metabolism. Specifically, SF2 RNA helicases, a subset of the DEAD-box family, are essential players in plant developmental processes and responses to biotic and abiotic stresses. Despite this, information on this family in the physic nut ( Jatropha curcas L.) remains limited, spanning from structural patterns to stress responses. We identified 79 genes encoding DEAD-box RNA helicases ( Jc DHX) in the J...

Standardized and thoroughly characterized genetic tools are a prerequisite for studying cellular processes to ensure the reusability and consistency of experimental results. The discovery of fluorescent proteins (FPs) represents a milestone in the development of genetic reporters for monitoring transcription or protein localization in vivo. FPs have revolutionized our understanding of cellular dynamics by enabling the real-time visualization and tracking of biological processes. Despite these advancements, challenges remain in the appropriate use of FPs, specifically regarding their proper application, protein turnover dynamics, and the undesired disruption of cellular functions...

Although the formation, turnover, and accumulation of soil organic carbon (SOC) are driven by different fertilizer inputs and their subsequent microbial-mediated transformation, the relationship between changes in plant-derived and microbial-derived components and soil microbial life history strategies under different fertilization regimes has not been well explored. In this study, the changes in microbial necromass carbon (MNC), lignin phenols, and glomalin-related soil protein (GRSP), as well as soil microbial life history strategy were determined in a 16-year field experiment in response to different fertilization regimes, including a no-fertilizer control (C), conventional chemical NPK fertilization (NPK), and partial substitutions of the NPK in chemical fertilizers with a low (30 %) or high (60 %) level of straw (0...

In humans and plants, 40% of the proteome is co-translationally acetylated at the N-terminus by a single Nα-acetyltransferase (Nat) termed NatA. The core NatA complex is comprised of the catalytic subunit Nα- acetyltransferase 10 (NAA10) and the ribosome-anchoring subunit NAA15. The regulatory subunit Huntingtin Yeast Partner K (HYPK) and the acetyltransferase NAA50 join this complex in humans. Even though both are conserved in Arabidopsis (Arabidopsis thaliana), only AtHYPK is known to interact with AtNatA...