Chaperones

Zebra mussel (ZM), Dreissena polymorpha , commonly used as a sentinel species in freshwater biomonitoring, is now in competition for habitat with quagga mussel (QM), Dreissena rostriformis bugensis. This raises the question of the quagga mussel's use in environmental survey. To better characterise QM response to stress compared with ZM, both species were exposed to cadmium (100 µg·L-1 ), a classic pollutant, for 7 days under controlled conditions. The gill proteomes were analysed using two-dimensional electrophoresis coupled with mass spectrometry...

Orb2 the Drosophila homolog of cytoplasmic polyadenylation element binding (CPEB) protein forms prion-like oligomers. These oligomers consist of Orb2A and Orb2B isoforms and their formation is dependent on the oligomerization of the Orb2A isoform. Drosophila with a mutation diminishing Orb2A's prion-like oligomerization forms long-term memory but fails to maintain it over time. Since this prion-like oligomerization of Orb2A plays a crucial role in the maintenance of memory, here, we aim to find what regulates this oligomerization...

Deep penetration and downregulation of heat shock protein (HSP) expression in multimodal synergistic therapy are promising approaches for curing cancer in clinical trials. However, free small-molecule drugs and most drug vehicles have a low delivery efficiency deep into the tumor owing to poor drug penetration and hypoxic conditions at the tumor site. In this study, the objective is to use reactive oxygen species (ROS)-responsive supramolecular gels co-loaded with the photosensitizer Zn(II) phthalocyanine tetrasulfonic acid (ZnPCS4 ) and functionalized tetrahedral DNA (TGSAs) (G@P/TGSAs) to enhance deep tissue and cell penetration and block the HSP90 pathway for chemo- photodynamic therapy (PDT) - photothermal therapy (PTT) trimodal synergistic therapy...

Heat shock protein 70 (HSP70) is a highly conserved protein functioning as a "molecular chaperone", which is integral to protein folding and maturation. In addition to its high expression within cells upon stressful challenges, HSP70 can be translocated to the cell membrane or released from cells in free form or within extracellular vesicles (EVs). Such trafficking of HSP70 is also present in cancer cells, as HSP70 is overexpressed in various types of patient samples across a range of common malignancies, signifying that extracellular HSP70 (eHSP70) can serve as a tumor biomarker...

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. According to the Braak hypothesis, the disease spreads along specific neuroanatomical pathways. Studies indicate that fibrillar alpha-synuclein (F-αSyn) can propagate from cell-to-cell by following intercellular connections, leading to the selective death of certain cell groups like substantia nigra dopaminergic neurons and advancing the pathology. Internalized F-αSyn can be eliminated by lysosomes, proteasomes, or chaperones before it replicates inside the cell...

Heat shock protein 90 (Hsp90) is a molecular chaperone important for maintaining protein homeostasis (proteostasis) in the cell. Hsp90 inhibitors are being explored as cancer therapeutics because of their ability to disrupt proteostasis. Inhibiting Hsp90 increases surface density of the immunological receptor Major Histocompatibility Complex 1 (MHC1). Here we show that this increase occurs across multiple cancer cell lines and with both cytosol-specific and pan-Hsp90 inhibitors. We demonstrate that Hsp90 inhibition also alters surface expression of both IFNGR and PD-L1, two additional immunological receptors that play a significant role in anti-tumour or anti-immune activity in the tumour microenvironment...

The intestine plays a key role in metabolism, nutrient and water absorption, and provides both physical and immunological defense against dietary and luminal antigens. The protective mucus lining in the intestine is a critical component of intestinal barrier function that when compromised, can lead to dysfunctional intestinal barriers that are a defining characteristic of inflammatory bowel disease (IBD), among other intestinal diseases. Here, we define a new role for the flavin-containing monooxygenase family of enzymes in maintaining a healthy intestinal epithelium...

Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins from Drosophila CNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms...

UNLABELLED: Microtubules (MTs) are dynamic components of the cytoskeleton and play essential roles in morphogenesis and maintenance of tissue and cell integrity. Despite recent advances in understanding MT ultrastructure, organization, and growth control, how cells regulate MT organization at the cell cortex remains poorly understood. The EFA-6/EFA6 proteins are recently identified membrane-associated proteins that inhibit cortical MT dynamics. Here, combining visualization of endogenously tagged C...

The intricate protein-chaperone network is vital for cellular function. Recent discoveries have unveiled the existence of specialized chaperone complexes called epichaperomes, protein assemblies orchestrating the reconfiguration of protein-protein interaction networks, enhancing cellular adaptability and proliferation. This study delves into the structural and regulatory aspects of epichaperomes, with a particular emphasis on the significance of post-translational modifications in shaping their formation and function...

Although all herpesviruses utilize a highly conserved replication machinery to amplify their viral genomes, different members may have unique strategies to modulate the assembly of their replication components. Herein, we characterize the subcellular localization of seven essential replication proteins of varicella-zoster virus (VZV) and show that several viral replication enzymes such as the DNA polymerase subunit ORF28, when expressed alone, are localized in the cytoplasm. The nuclear import of ORF28 can be mediated by the viral DNA polymerase processivity factor ORF16...

The proteostasis network and associated protein quality control (PQC) mechanisms ensure proteome functionality and are essential for cell survival. A distinctive feature of eukaryotic cells is their high degree of compartmentalization, requiring specific and adapted proteostasis networks for each compartment. The nucleus, essential for maintaining the integrity of genetic information and gene transcription, is one such compartment. While PQC mechanisms have been investigated for decades in the cytoplasm and the endoplasmic reticulum, our knowledge of nuclear PQC pathways is only emerging...

Heavy metal stress is a major problem in present scenario and the consequences are well known. The agroecosystems are heavily affected by the heavy metal stress and the question arises on the sustainability of the agricultural products. Heavy metals inhibit the process to influence the reactive oxygen species production. When abundantly present copper metal ion has toxic effects which is mitigated by the exogenous application of Si. The role of silicon is to enhance physical parameters as well as gas exchange parameters...

Glucocerebrosidase 1 (GBA1) mutations are the most important genetic risk factors for Parkinson's disease (PD). Clinically, mild (e.g., p.N370S) and severe (e.g., p.L444P and p.D409H) GBA1 mutations have different PD phenotypes, with differences in age at disease onset, progression, and the severity of motor and non-motor symptoms. We hypothesize that GBA1 mutations cause the accumulation of α-synuclein by affecting the cross-talk between cellular protein degradation mechanisms, leading to neurodegeneration...

No abstract text is available yet for this article.

The Hypoxia-Inducible Factor 1 (HIF-1) is essential for cellular adaptation to reduced oxygen levels. It also facilitates the maintenance and re-establishment of skin homeostasis. Among others, it is involved in regulating keratinocyte differentiation. The stability of the oxygen-liable HIF-1α subunit is regulated by various non-canonical oxygen-independent mechanisms, which among others involve Heat Shock Proteins of the A family (HSPA/HSP70). This group of highly homologous chaperones and proteostasis-controlling factors includes HSPA2, a unique member crucial for spermatogenesis and implicated in the regulation of keratinocyte differentiation...

The modification of nuclear, cytoplasmic, and mitochondrial proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is an essential post-translational modification common in metazoans. O-GlcNAc is cycled on and off proteins in response to environmental and physiological stimuli impacting protein function, which, in turn, tunes pathways that include transcription, translation, proteostasis, signal transduction, and metabolism. One class of stimulus that induces rapid and dynamic changes to O-GlcNAc is cellular injury, resulting from environmental stress (for instance, heat shock), hypoxia/reoxygenation injury, ischemia reperfusion injury (heart attack, stroke, trauma hemorrhage), and sepsis...

The heat shock transcription factors Hsf1 and Hsf2 have been studied since many years mainly in the context of stress response and in malignant cells. Their physiological function in non-malignant human cells under non-stress conditions is still largely unknown. To approach this important issue, Joutsen et al. present immunohistochemical staining data on Hsf1 and Hsf2 in 80 non-pathological human tissue samples. The wealth of these data elicits many interesting questions that will spur many future research projects...

We talk to first and last authors Guy Zoltsman and Rina Rosenzweig about their paper, "A unique chaperoning mechanism in Class A JDPs recognizes and stabilizes mutant p53," how every result may be important in the right context, and the importance to Rina that her lab is an encouraging and collaborative place.

Regulation of the oxidative stress response is crucial for the management and prognosis of traumatic brain injury (TBI). The copper chaperone Antioxidant 1 (Atox1) plays a crucial role in regulating intracellular copper ion balance and impacting the antioxidant capacity of mitochondria, as well as the oxidative stress state of cells. However, it remains unknown whether Atox1 is involved in modulating oxidative stress following TBI. Here, we investigated the regulatory role of Atox1 in oxidative stress on neurons both in vivo and in vitro, and elucidated the underlying mechanism through culturing hippocampal HT-22 cells with Atox1 mutation...