Endogenous IFN ‐γ facilitates Pneumocystis infection and downregulates carbohydrate receptors in CD4+ T cell‐depleted mice
IFN- γ attenuates phagocytic activity of alveolar macrophages againstPneumocystis organisms by downregulating the expression of Dectin-1 and macrophage mannose receptor (MMR) in immunocompromised subjects. IFN- γ plays a critical role in host defense against intracellular pathogens. IFN-γ is produced in the bronchoalveolar lavage fluid of mice infected withPneumocystis, but the role of IFN- γ in host defense againstPneumocystis remains controversial. It has been previously reported that although exogenous IFN- γ has beneficial effects on eradication ofPneumocystis, endogenous IFN- γ has a negative impact on innate im...
Source: FEBS Letters - April 18, 2024 Category: Biochemistry Authors: Yi Wang,
Hisashi Nagase,
Yoh ‐ichi Tagawa,
Shinsuke Taki,
Masaya Takamoto Tags: Research Letter Source Type: research
Molecular dynamics simulations of intracellular lipid droplets: a new tool in the toolbox
In thisPerspective review, we offer a comprehensive overview of computational studies on lipid droplets biology, with a specific focus on molecular dynamics simulations. Revisiting key contributions, we highlight the pivotal role of these studies in advancing our understanding of lipid droplets, for both mechanistic and physiological aspects. Lipid droplets (LDs) are ubiquitous intracellular organelles with a central role in multiple lipid metabolic pathways. However, identifying correlations between their structural properties and their biological activity has proved challenging, owing to their unique physicochemical prop...
Source: FEBS Letters - April 17, 2024 Category: Biochemistry Authors: Jennifer Sapia,
Stefano Vanni Tags: Perspective Source Type: research
iChIP ‐SILAC analysis identifies epigenetic regulators of CpG methylation of the p16INK4A gene
iChIP-SILAC identified DNMT1 and epigenetic regulators as proteins potentially interacting with a region of thep16INK4A gene that is CpG-methylated in one allele in HCT116 cells. Among the identified proteins, DDX24 contributed to the CpG methylation by regulating the protein level of DNMT1. iChIP is useful to identify proteins binding to a target locus. Allele-specific epigenetic events regulate the expression of specific genes such as tumor suppressor genes. Methods to biochemically identify epigenetic regulators remain limited. Here, we used insertional chromatin immunoprecipitation (iChIP) to address this issue. iChIP ...
Source: FEBS Letters - April 17, 2024 Category: Biochemistry Authors: Toshitsugu Fujita,
Hodaka Fujii Tags: Research Article Source Type: research
Why an integrated view of gene expression studies on hematopoiesis in mouse aging is better than the sum of their parts
A standard approach to studying aging in mice typically involves the isolation of hematopoietic stem cells from two cohorts, namely young and old, from which total RNA is extracted, sequenced, and analyzed through R-based standard protocols. The lists of differentially expressed genes resulting from these analyses are usually interpreted with Gene Ontology classifications. Globally, the human population is aging, with an increased proportion of people in “old age” (over 60 years). This trend leads to a growing demand in aging research, stimulating studies in animal models such as mice, fish, and invertebrates. Recent...
Source: FEBS Letters - April 17, 2024 Category: Biochemistry Authors: Leonid V. Bystrykh Tags: Perspective Source Type: research
Ngk1 kinase ‐mediated N‐acetylglucosamine metabolism promotes UDP‐GlcNAc biosynthesis in Saccharomyces cerevisiae
We uncovered a novel pathway ofN-acetylglucosamine (GlcNAc) metabolism for uridine diphosphateN-acetylglucosamine (UDP-GlcNAc) biosynthesis via Ngk1 kinase inSaccharomyces cerevisiae. GlcNAc phosphorylation by Ngk1 promotes UDP-GlcNAc synthesis and compensates for the hexosamine pathway, a known pathway for UDP-GlcNAc synthesis. The increased synthesis of UDP-GlcNAc by Ngk1 enhances chitin production. N-acetylglucosamine (GlcNAc) is an important structural component of the cell wall chitin,N-glycans, glycolipids, and GPI-anchors in eukaryotes. GlcNAc kinase phosphorylates GlcNAc into GlcNAc-6-phosphate, a precursor of urid...
Source: FEBS Letters - April 16, 2024 Category: Biochemistry Authors: Ayano Nishikawa,
Shuichi Karita,
Midori Umekawa Tags: Research Letter Source Type: research
PAT mRNA decapping factors are required for proper development in Arabidopsis
In conclusion, PATs exhibit both specific and redundant functions during different plant growth stages and our observations underpin the selective regulation of the mRNA decay machinery for proper development. (Source: FEBS Letters)
Source: FEBS Letters - April 12, 2024 Category: Biochemistry Authors: Zhangli Zuo,
Milena Edna Roux,
Yasin F. Dagdas,
Eleazar Rodriguez,
Morten Petersen Tags: Research Letter Source Type: research
The components of the AhR ‐molecular chaperone complex differ depending on whether the ligands are toxic or non‐toxic
When bound to toxic or non-toxic ligands, aryl hydrocarbon receptors (AhRs) are activated and nuclear translocation occurs; AhRs are bound to molecular chaperone complexes, AhR-HSP90-XAP2-p23 for toxic ligands, whereas for non-toxic ligands AhR-HSP90- XAP2 for non-toxic ligands. Toxic and non-toxic ligand selectivity of AhR depends on the components of the molecular chaperone complex. The aryl hydrocarbon receptor (AhR) forms a complex with the HSP90-XAP2-p23 molecular chaperone when the cells are exposed to toxic compounds. Recently, 1,4-dihydroxy-2-naphthoic acid (DHNA) was reported to be an AhR ligand. Here, we investig...
Source: FEBS Letters - April 12, 2024 Category: Biochemistry Authors: Yukihiko Narita,
Arisa Tamura,
Shiori Hatakeyama,
Seiya Uemura,
Atsuko Miura,
Asami Haga,
Noriko Tsuji,
Nozomi Fujie,
Yukina Izumi,
Taku Sugawara,
Michiro Otaka,
Ken Okamoto,
Peng Lu,
Suguru Okuda,
Michio Suzuki,
Koji Nagata,
Hiroaki Shimi Tags: Research Letter Source Type: research
The lipid droplet lipidome
Lipid droplets act as active gatekeepers in lipid quality control, capable of orchestrating intra- and extra-cellular lipid fluxes. Numerous examples indicate the intrinsic link between LD lipids and proteins, calling for a deeper characterization of the LD lipidome. Here, we reviewed the current knowledge of LD lipidome composition with a brief overview of lipids present within the neutral core and phospholipid monolayer. Lipid droplets (LDs) are intracellular organelles with a hydrophobic core formed by neutral lipids surrounded by a phospholipid monolayer harboring a variety of regulatory and enzymatically active protei...
Source: FEBS Letters - April 12, 2024 Category: Biochemistry Authors: Michele W ölk,
Maria Fedorova Tags: Review Source Type: research
κB‐Ras proteins are fast‐exchanging GTPases and function via nucleotide‐independent binding of Ral GTPase‐activating protein complexes
Contrary to previous predictions, we provide evidence that the small GTPase κB-Ras possesses intrinsic hydrolytic activity. However, low nucleotide affinity leads to fast nucleotide exchange and renders κB-Ras constitutively GTP-bound in cells. We characterize κB-Ras mutations occurring in tumors and define that nucleotide binding supports protein stability but is not re quired for a constitutive noneffector interaction with RalGAP complexes. κB-Ras (NF-κB inhibitor-interacting Ras-like protein) GTPases are small Ras-like GTPases but harbor interesting differences in important sequence motifs. They act in a tumor-supp...
Source: FEBS Letters - April 12, 2024 Category: Biochemistry Authors: Ren é Rasche,
Lisa Helene Apken,
Esther Michalke,
Daniel Kümmel,
Andrea Oeckinghaus Tags: Research Letter Source Type: research
Characterization of the endogenous retrovirus ‐derived placenta‐specific soluble protein EnvV‐Fca from domestic cats
This study suggests that birds, bats, and rodents carrying EnvV2 may play significant roles as intermediate vectors in spreading or cross-transmitting viruses among species. Our findings provide valuable insights into the evolution of ERV in vertebrate hosts. (Source: FEBS Letters)
Source: FEBS Letters - April 12, 2024 Category: Biochemistry Authors: Didik Pramono,
Kenji Sugimoto,
Tohru Kimura,
Ariko Miyake,
Kazuo Nishigaki Tags: Research Article Source Type: research
Rejuvenating aged stem cells: therapeutic strategies to extend health and lifespan
Aging is associated with an impairment in stem cell function and several strategies for stem cell rejuvenation have been proposed: exercise, dietary restriction, reprogramming, senolytics, increasing autophagy, youthful blood factors exchange, and restoring cell polarity. Here, we review these strategies and their effects on rejuvenating stem cells in different tissues and underline when stem cell rejuvenation was able to improve health and lifespan. Aging is associated with a global decline in stem cell function. To date, several strategies have been proposed to rejuvenate aged stem cells: most of these result in function...
Source: FEBS Letters - April 12, 2024 Category: Biochemistry Authors: Francesca Matteini,
Sara Montserrat ‐Vazquez,
M. Carolina Florian Tags: In a Nutshell Source Type: research
The DMT1 isoform lacking the iron ‐response element regulates normal and malignant hematopoiesis via NOTCH pathway activation
In this report, we investigated the function of DMT1 nonIRE in normal and malignant hematopoiesis. Knockdown of Dmt1 nonIRE in mice showed that it has non-canonical functions in hematopoietic stem cell differentiation: its knockdown suppressed development along the myeloid and lymphoid lineages, while promoting the production of platelets. These phenotypic effects on the hematopoietic system induced by Dmt1 nonIRE knockdown were linked to suppression of Notch/Myc pathway activity. Conversely, our data indicate a non-canonical function for DMT1 nonIRE overexpression in boosting NOTCH pathway activity in T-cell leukemia home...
Source: FEBS Letters - April 10, 2024 Category: Biochemistry Authors: Judith Hounjet,
Linde Van Aerschot,
Kim De Keersmaecker,
Marc Vooijs,
Kim R. Kampen Tags: Research Letter Source Type: research
OTUD6A orchestrates complex modulation of TEAD4 ‐mediated transcriptional programs
In this study, we focused on transcriptional enhancer factor TEF-3 (TEAD4), exploring its regulation by the deubiquitinase OTU domain-containing protein 6A (OTUD6A). We identified OTUD6A as a TEAD4-interacting deubiquitinase, positively influencing TEAD-driven transcription without altering TEAD4 stability. Structural analyses revealed specific interaction domains: the N-terminal domain of OTUD6A and the YAP-binding domain of TEAD4. Functional assays demonstrated the positive impact of OTUD6A on the transcription of YAP –TEAD target genes. Despite no impact on TEAD4 nuclear localization, OTUD6A selectively modulated nucl...
Source: FEBS Letters - April 10, 2024 Category: Biochemistry Authors: Hyo Jin Kim,
Yunsik Choi,
Yuri Lee,
Mi Hwangbo,
Jongchan Kim Tags: Research Article Source Type: research
Hepatitis B virus ‐specific human stem cell memory T cells differentiate into cytotoxic T cells and eradicate HBV‐infected hepatocytes in mice
Here, we detected stem cell memory T cells (TSCMs) in chronic hepatitis B virus (HBV)-infected patients, using HBV core and polymerase peptide HLA tetramers. When these TSCMs were transferred into the human hepatocyte-transplanted, HBV-infected TK-NOG mouse, they differentiated into cytotoxic T lymphocytes, produced interferon gamma and interleukin-2, and developed histologically proven hepatitis. Furthermore, HBV DNA and human albumin in mouse serum declined and human hepatocytes were eliminated in the mouse model. Chronic infection with the hepatitis B virus (HBV) induces progressive hepatic impairment. Achieving complet...
Source: FEBS Letters - April 10, 2024 Category: Biochemistry Authors: Hiromi Abe ‐Chayama,
Takakazu Kawase,
Tatsuo Ichinohe,
Yuji Ishida,
Chise Tateno,
Makoto Hijikata,
Kazuaki Chayama Tags: Research Letter Source Type: research
Structural determinants for membrane binding of the EGFR juxtamembrane domain
The region containing residues I649 − L659 of the epidermal growth factor receptor (EGFR) juxtamembrane domain (JM) specifically interacts with PI(4,5)P2-or phosphatidylserine-containing membranes, suggesting that membrane binding may affect JM dimerization and, therefore, regulate EGFR kinase activation. Overactivation of the epidermal growth factor receptor (EGFR) is critical for the development of multiple cancers. Previous studies have shown that the cell membrane is a key regulator of EGFR kinase activity through its interaction with the EGFR juxtamembrane domain (JM). However, the lipid recognition specificity...
Source: FEBS Letters - April 9, 2024 Category: Biochemistry Authors: Ziwei Wu,
Ling Li,
Lina Zhu,
Runhan Wang,
Yingkui Dong,
Yaoyao Zhang,
Yujuan Wang,
Junfeng Wang,
Lei Zhu Tags: Research Letter Source Type: research
