Microbiological Research, Journal Year: 2024, Volume and Issue: 290, P. 127940 - 127940
Published: Nov. 8, 2024
Language: Английский
Life, Journal Year: 2025, Volume and Issue: 15(1), P. 126 - 126
Published: Jan. 18, 2025
Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations environmental stressors, on one hand, cancer cell structure, functioning, behavior. Aberrant PTMs can be considered as enabling characteristics long they orchestrate all malignant variability in proteome cells, cancer-associated tumor microenvironment (TME). On other enhance anticancer mechanisms tumoral ecosystem or sustain beneficial effects oncologic therapies through degradation inactivation carcinogenic or/and activation tumor-suppressor proteins. In this review, we summarized analyzed a wide spectrum involved regulatory that drive tumorigenesis, genetic instability, epigenetic reprogramming, events metastatic cascade, cytoskeleton extracellular matrix (ECM) remodeling, angiogenesis, immune response, tumor-associated microbiome, metabolism rewiring most important hallmarks cancer. All develop due to proteins, which modulate gene transcription, intracellular signaling, protein size, activity, stability localization, trafficking, secretion, half-life, protein–protein interactions (PPIs). associated with exploited better understand underlying molecular heterogeneous chameleonic disease, find new biomarkers progression prognosis, personalize oncotherapies, discover targets for drug development.
Language: Английский
Citations
2
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Journal Year: 2024, Volume and Issue: 1872(4), P. 141017 - 141017
Published: April 18, 2024
The diversity and dynamics of proteins play essential roles in maintaining the basic constructions functions cells. abundance functional is regulated by transcription translation processes, while alternative splicing enables same gene to generate distinct protein isoforms different lengths. Beyond transcriptional translational regulations, post-translational modifications (PTMs) are able further expand scope proteins. PTMs have been shown make significant changes surface charges, structures, activation states, interactome Due complexity, highly dynamic nature, low presence percentage, study remains challenging. Here we summarize discuss major chemical biology tools proteomics approaches enrich investigate PTM interest.
Language: Английский
Citations
10
Planta, Journal Year: 2024, Volume and Issue: 260(4)
Published: Sept. 12, 2024
Language: Английский
Citations
5
FEBS Journal, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 5, 2025
RING‐type E3 ubiquitin ligases promote ubiquitylation by stabilising an active complex between a ubiquitin‐loaded E2‐conjugating enzyme and protein substrate. To fulfil this function, the ubiquitin‐protein ligase SIAH1 other SINA/SIAH subfamily employ N‐terminal catalytic RING domain C‐terminal substrate‐binding (SBD), separated two zinc fingers. Here, we present first crystal structure of human SIAH1, together with adjacent finger, revealing potential dimer, which was validated in solution using static light scattering. dimerisation contributes to activity both vitro cells. Moreover, as is second element, after SBD, independently favour homodimerisation within ligases, propose that alternating RING:RING SBD:SBD interactions organise multiple copies into higher‐order homomultimer. In line hypothesis, fluorescently tagged full‐length SIAH2 fruit fly SINA show cytoplasmic clusters cells, whereas their distribution becomes more diffuse when disabled. The wild‐type (WT) form but not its mutant, colocalises aggregated synphilin‐1A under proteasomal inhibition, suggesting multimerisation might contribute reported preference for or multimeric substrates.
Language: Английский
Citations
0
Biochemistry, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 26, 2025
Phosphorylation is a reversible post-translational modification that can modulate protein function. For example, phosphorylation modifications of solute carrier family 12 (SLC12) proteins function as molecular switches precisely regulate cation–chloride ion transport. Elucidating the phosphoregulatory mechanism SLC12 at carboxy-terminal domain (CTD) through structural determination approaches remains challenging due to domain's disordered and flexible nature. In this study, dynamics (MD) simulations enhanced sampling techniques were employed investigate CTD SLC12A6 (also known KCC3). Atomistic MD metadynamics revealed dephosphorylation residues T940 T997 stabilizes favorable state "switches on" solvent accessibility inward-facing pocket. Meanwhile, induces distinct orientations CTD, transitioning dimer into another off" accessibility. The alteration in pocket influences water dynamics. Based on these findings, we propose "knob switch" model illustrate how regulates transport KCC3.
Language: Английский
Citations
0
Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 390 - 390
Published: March 26, 2025
Fibrinogen, a pivotal plasma glycoprotein, plays an essential role in hemostasis by serving as the precursor to fibrin, which forms structural framework of blood clots. Beyond coagulation, fibrinogen influences immune responses, inflammation, and tissue repair. Oxidative stress, characterized imbalance between reactive oxygen species (ROS) antioxidants, induces oxidation, significantly altering its structure function. This narrative review synthesizes findings from vitro, ex vivo, clinical studies, emphasizing impact oxidation on clot formation, architecture, degradation. modifications result denser fibrin clots with thinner fibers, reduced permeability, heightened resistance fibrinolysis. These changes exacerbate prothrombotic conditions cardiovascular diseases, diabetes, chronic inflammatory disorders cancer. In contrast, “low-dose” oxidative stress may elicit protective adaptations fibrinogen, preserving The also highlights discrepancies experimental due variability protocols patient conditions. Understanding interplay function could unveil therapeutic strategies targeting stress. Antioxidant therapies or selective inhibitors detrimental hold potential for mitigating thrombotic risks. However, further research is pinpoint specific sites, clarify their roles dynamics, bridge gap basic practice.
Language: Английский
Citations
0
npj Aging, Journal Year: 2025, Volume and Issue: 11(1)
Published: March 30, 2025
Skeletal muscle weakness is a major component of age-associated frailty, but the underlying mechanisms are not completely understood. Drosophila has emerged as useful model for studying skeletal aging. In this organism, previous lab-based selection established strains with increased longevity and reduced functional decline compared to parental strain. Here, we have applied computational pipeline (JUMPptm) retrieving information on 8 post-translational modifications (PTMs) from proteomes 2 long-lived corresponding strain in young old age. This pan-PTM analysis identified 2470 modified sites (acetylation, carboxylation, deamidation, dihydroxylation, mono-methylation, oxidation, phosphorylation, ubiquitination) several classes proteins, including evolutionarily conserved contractile proteins metabolic enzymes. PTM consensus sequences further highlight amino acids that enriched adjacent site, thus providing insight into flanking residues influence distinct PTMs. Altogether, these analyses identify PTMs associated during aging may underlie negligible senescence lab-evolved strains.
Language: Английский
Citations
0
Phytomedicine, Journal Year: 2024, Volume and Issue: 135, P. 156192 - 156192
Published: Oct. 30, 2024
Language: Английский
Citations
1
Microbiological Research, Journal Year: 2024, Volume and Issue: 290, P. 127940 - 127940
Published: Nov. 8, 2024
Language: Английский
Citations
0