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1.
Bioinformatic and experimental characterization of SEN1998: a conserved gene carried by the Enterobacteriaceae-associated ROD21-like family of genomic islands.
Piña-Iturbe, A, Hoppe-Elsholz, G, Fernández, PA, Santiviago, CA, González, PA, Bueno, SM
Scientific reports. 2022;(1):2435
Abstract
Genomic islands (GIs) are horizontally transferred elements that shape bacterial genomes and contributes to the adaptation to different environments. Some GIs encode an integrase and a recombination directionality factor (RDF), which are the molecular GI-encoded machinery that promotes the island excision from the chromosome, the first step for the spread of GIs by horizontal transfer. Although less studied, this process can also play a role in the virulence of bacterial pathogens. While the excision of GIs is thought to be similar to that observed in bacteriophages, this mechanism has been only studied in a few families of islands. Here, we aimed to gain a better understanding of the factors involved in the excision of ROD21 a pathogenicity island of the food-borne pathogen Salmonella enterica serovar Enteritidis and the most studied member of the recently described Enterobacteriaceae-associated ROD21-like family of GIs. Using bioinformatic and experimental approaches, we characterized the conserved gene SEN1998, showing that it encodes a protein with the features of an RDF that binds to the regulatory regions involved in the excision of ROD21. While deletion or overexpression of SEN1998 did not alter the expression of the integrase-encoding gene SEN1970, a slight but significant trend was observed in the excision of the island. Surprisingly, we found that the expression of both genes, SEN1998 and SEN1970, were negatively correlated to the excision of ROD21 which showed a growth phase-dependent pattern. Our findings contribute to the growing body of knowledge regarding the excision of GIs, providing insights about ROD21 and the recently described EARL family of genomic islands.
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2.
Nitric oxide, gravity response, and a unified schematic of plant signaling.
Kruse, CPS, Wyatt, SE
Plant science : an international journal of experimental plant biology. 2022;:111105
Abstract
Plant signaling components are often involved in numerous processes. Calcium, reactive oxygen species, and other signaling molecules are essential to normal biotic and abiotic responses. Yet, the summation of these components is integrated to produce a specific response despite their involvement in a myriad of response cascades. In the response to gravity, the role of many of these individual components has been studied, but a specific sequence of signals has not yet been assembled into a cohesive schematic of gravity response signaling. Herein, we provide a review of existing knowledge of gravity response and differential protein and gene regulation induced by the absence of gravity stimulus aboard the International Space Station and propose an integrated theoretical schematic of gravity response incorporating that information. Recent developments in the role of nitric oxide in gravity signaling provided some of the final contextual pillars for the assembly of the model, where nitric oxide and the role of cysteine S-nitrosation may be central to the gravity response. The proposed schematic accounts for the known responses to reorientation with respect to gravity in roots-the most well studied gravitropic plant tissue-and is supported by the extensive evolutionary conservation of regulatory amino acids within protein components of the signaling schematic. The identification of a role of nitric oxide in regulating the TIR1 auxin receptor is indicative of the broader relevance of the schematic in studying a multitude of environmental and stress responses. Finally, there are several experimental approaches that are highlighted as essential to the further study and validation of this schematic.
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3.
BAG3 is a negative regulator of ciliogenesis in glioblastoma and triple-negative breast cancer cells.
Linder, B, Klein, C, Hoffmann, ME, Bonn, F, Dikic, I, Kögel, D
Journal of cellular biochemistry. 2022;(1):77-90
Abstract
By regulating several hallmarks of cancer, BAG3 exerts oncogenic functions in a wide variety of malignant diseases including glioblastoma (GBM) and triple-negative breast cancer (TNBC). Here we performed global proteomic/phosphoproteomic analyses of CRISPR/Cas9-mediated isogenic BAG3 knockouts of the two GBM lines U343 and U251 in comparison to parental controls. Depletion of BAG3 evoked major effects on proteins involved in ciliogenesis/ciliary function and the activity of the related kinases aurora-kinase A and CDK1. Cilia formation was significantly enhanced in BAG3 KO cells, a finding that could be confirmed in BAG3-deficient versus -proficient BT-549 TNBC cells, thus identifying a completely novel function of BAG3 as a negative regulator of ciliogenesis. Furthermore, we demonstrate that enhanced ciliogenesis and reduced expression of SNAI1 and ZEB1, two key transcription factors regulating epithelial to mesenchymal transition (EMT) are correlated to decreased cell migration, both in the GBM and TNBC BAG3 knockout cells. Our data obtained in two different tumor entities identify suppression of EMT and ciliogenesis as putative synergizing mechanisms of BAG3-driven tumor aggressiveness in therapy-resistant cancers.
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4.
Plant adaptation to low phosphorus availability: Core signaling, crosstalks, and applied implications.
Paz-Ares, J, Puga, MI, Rojas-Triana, M, Martinez-Hevia, I, Diaz, S, Poza-Carrión, C, Miñambres, M, Leyva, A
Molecular plant. 2022;(1):104-124
Abstract
Phosphorus (P) is an essential nutrient for plant growth and reproduction. Plants preferentially absorb P as orthophosphate (Pi), an ion that displays low solubility and that is readily fixed in the soil, making P limitation a condition common to many soils and Pi fertilization an inefficient practice. To cope with Pi limitation, plants have evolved a series of developmental and physiological responses, collectively known as the Pi starvation rescue system (PSR), aimed to improve Pi acquisition and use efficiency (PUE) and protect from Pi-starvation-induced stress. Intensive research has been carried out during the last 20 years to unravel the mechanisms underlying the control of the PSR in plants. Here we review the results of this research effort that have led to the identification and characterization of several core Pi starvation signaling components, including sensors, transcription factors, microRNAs (miRNAs) and miRNA inhibitors, kinases, phosphatases, and components of the proteostasis machinery. We also refer to recent results revealing the existence of intricate signaling interplays between Pi and other nutrients and antagonists, N, Fe, Zn, and As, that have changed the initial single-nutrient-centric view to a more integrated view of nutrient homeostasis. Finally, we discuss advances toward improving PUE and future research priorities.
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5.
Role of the AMPK signalling pathway in the aetiopathogenesis of ocular diseases.
Shukal, DK, Malaviya, PB, Sharma, T
Human & experimental toxicology. 2022;:9603271211063165
Abstract
BACKGROUND AMP-activated protein kinase (AMPK) plays a precise role as a master regulator of cellular energy homeostasis. AMPK is activated in response to the signalling cues that exhaust cellular ATP levels such as hypoxia, ischaemia, glucose depletion and heat shock. As a central regulator of both lipid and glucose metabolism, AMPK is considered to be a potential therapeutic target for the treatment of various diseases, including eye disorders. OBJECTIVE To review all the shreds of evidence concerning the role of the AMPK signalling pathway in the pathogenesis of ocular diseases. METHOD Scientific data search and review of available information evaluating the influence of AMPK signalling on ocular diseases. RESULTS Review highlights the significance of AMPK signalling in the aetiopathogenesis of ocular diseases, including cataract, glaucoma, diabetic retinopathy, retinoblastoma, age-related macular degeneration, corneal diseases, etc. The review also provides the information on the AMPK-associated pathways with reference to ocular disease, which includes mitochondrial biogenesis, autophagy and regulation of inflammatory response. CONCLUSION The study concludes the role of AMPK in ocular diseases. There is growing interest in the therapeutic utilization of the AMPK pathway for ocular disease treatment. Furthermore, inhibition of AMPK signalling might represent more pertinent strategy than AMPK activation for ocular disease treatment. Such information will guide the development of more effective AMPK modulators for ocular diseases.[Formula: see text].
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6.
FOXO1 forkhead domain mutants in B-cell lymphoma lack transcriptional activity.
Sablon, A, Bollaert, E, Pirson, C, Velghe, AI, Demoulin, JB
Scientific reports. 2022;(1):1309
Abstract
Somatic point mutations of the FOXO1 transcription factor were reported in non-Hodgkin lymphoma including diffuse large B-cell lymphoma, follicular lymphoma and Burkitt lymphoma. These alterations were associated with a poor prognosis and resistance to therapy. Nearly all amino acid substitutions are localized in two major clusters, affecting either the N-terminal region (Nt mutations) or the forkhead DNA-binding domain (DBD mutations). While recent studies have focused on Nt mutations, we characterized FOXO1 DBD mutants. We analyzed their transcriptional activity, DNA binding, phosphorylation and protein-protein interaction. The majority of DBD mutants showed a decrease in activity and DNA binding, while preserving AKT phosphorylation and interaction with the cytoplasmic ATG7 protein. In addition, we investigated the importance of conserved residues of the α-helix 3 of the DBD. Amino acids I213, R214, H215 and L217 appeared to be crucial for FOXO1 activity. Our data underlined the key role of multiple amino-acid residues of the forkhead domain in FOXO1 transcriptional activity and revealed a new type of FOXO1 loss-of-function mutations in B-cell lymphoma.
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7.
Inhibitory effect of polyphenols (phenolic acids, lignans, and stilbenes) on cancer by regulating signal transduction pathways: a review.
Hazafa, A, Iqbal, MO, Javaid, U, Tareen, MBK, Amna, D, Ramzan, A, Piracha, S, Naeem, M
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2022;(3):432-445
Abstract
Natural products, especially polyphenols (phenolic acids, lignans, and stilbenes) are suggested to be more potent anticancer drugs because of their no or less adverse effects, excess availability, high accuracy, and secure mode of action. In the present review, potential anticancer mechanisms of action of some polyphenols including phenolic acids, lignans, and stilbenes are discussed based on clinical, epidemiological, in vivo, and in vitro studies. The emerging evidence revealed that phenolic acids, lignans, and stilbenes induced apoptosis in the treatment of breast (MCF-7), colon (Caco-2), lung (SKLU-1), prostate (DU-145 and LNCaP), hepatocellular (hepG-2), and cervical (A-431) cancer cells, cell cycle arrest (S/G2/M/G1-phases) in gastric (MKN-45 and MKN-74), colorectal (HCT-116), bladder (T-24 and 5637), oral (H-400), leukemic (HL-60 and MOLT-4) and colon (Caco-2) cancer cells, and inhibit cell proliferation against the prostate (PC-3), liver (LI-90), breast (T47D and MDA-MB-231), colon (HT-29 and Caco-2), cervical (HTB-35), and MIC-1 cancer cells through caspase-3, MAPK, AMPK, Akt, NF-κB, Wnt, CD95, and SIRT1 pathways. Based on accumulated data, we suggested that polyphenols could be considered as a viable therapeutic option in the treatment of cancer cells in the near future.
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8.
Inhibiting TGF-[Formula: see text] 1-Mediated Cellular Processes as an Effective Strategy for the Treatment of Pulmonary Fibrosis with Chinese Herbal Medicines.
Wang, J, Zhao, X, Feng, W, Li, Y, Peng, C
The American journal of Chinese medicine. 2021;(8):1965-1999
Abstract
Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease that even threatens the lives of some patients infected with COVID-19. PF is a multicellular pathological process, including the initial injuries of epithelial cells, recruitment of inflammatory cells, epithelial-mesenchymal transition, activation and differentiation of fibroblasts, etc. TGF-[Formula: see text]1 acts as a key effect factor that participates in these cellular processes of PF. Recently, much attention was paid to inhibiting TGF-[Formula: see text]1 mediated cell processes in the treatment of PF with Chinese herbal medicines (CHM), an important part of traditional Chinese medicine. Here, this review first summarized the effects of TGF-[Formula: see text]1 in different cellular processes of PF. Then, this review summarized the recent research on CHM (compounds, multi-components, single medicines and prescriptions) to directly and/or indirectly inhibit TGF-[Formula: see text]1 signaling (TLRs, PPARs, micrRNA, etc.) in PF. Most of the research focused on CHM natural compounds, including but not limited to alkaloids, flavonoids, phenols and terpenes. After review, the research perspectives of CHM on TGF-[Formula: see text]1 inhibition in PF were further discussed. This review hopes that revealing the inhibiting effects of CHM on TGF-[Formula: see text]1-mediated cellular processes of PF can promote CHM to be better understood and utilized, thus transforming the therapeutic activities of CHM into practice.
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9.
TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation.
Magno, L, Bunney, TD, Mead, E, Svensson, F, Bictash, MN
Molecular neurodegeneration. 2021;(1):22
Abstract
The central role of the resident innate immune cells of the brain (microglia) in neurodegeneration has become clear over the past few years largely through genome-wide association studies (GWAS), and has rapidly become an active area of research. However, a mechanistic understanding (gene to function) has lagged behind. That is now beginning to change, as exemplified by a number of recent exciting and important reports that provide insight into the function of two key gene products - TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) and PLCγ2 (Phospholipase C gamma2) - in microglia, and their role in neurodegenerative disorders. In this review we explore and discuss these recent advances and the opportunities that they may provide for the development of new therapies.
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10.
Molecular trafficking between bacteria determines the shape of gut microbial community.
Boopathi, S, Liu, D, Jia, AQ
Gut microbes. 2021;(1):1959841
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Abstract
Complex inter-bacterial interactions largely influence the structure and function of the gut microbial community. Though several host-associated phenomena have often been shown to be involved in the stability, structure, and function of the gut microbial community, the implication of contact-dependent and contact-independent inter-bacterial interactions has been overlooked. Such interactions are tightly governed at multiple layers through several extracellular organelles, including contact-dependent inhibition (CDI), nanotubes, type VI secretion system (T6SS), and membrane vesicles (MVs). Recent advancements in molecular techniques have revealed that such extracellular organelles function beyond exhibiting competitive behavior and are also involved in manifesting cooperative behaviors. Cooperation between bacteria occurs through the sharing of several beneficial molecules including nucleic acids, proteins, metabolites, and nutrients among the members of the community, while competition occurs by means of multiple toxins. Intrinsic coordination between contact-dependent and contact-independent mechanisms collectively provides a fitness advantage and increased colonization resistance to the gut microbiota, where molecular trafficking plays a key role. This review is intended to provide a comprehensive view of the salient features of the different bacterial interactions and to highlight how microbiota deploy multifaceted organelles, for exerting both cooperative and competitive behaviors. We discuss the current knowledge of bacterial molecular trafficking and its impact on shaping the gut microbial community.