Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma

PROTEOMICS, Год журнала: 2023, Номер 23(9)

Опубликована: Янв. 10, 2023

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often metastasizes to lungs. The implications lysine lactylation (Kla), a recently identified histone post-translational modification (PTM), in pathology HCC remain unclear. Here, we report first proteomic survey this specific (with no metastasis during 3 years follow-up), normal tissues, and lung samples HCC. Of 2045 sites detected on 960 proteins, 1438 772 proteins contained quantitative information. Subsequently, analyzed differentially modified among different groups. Differentially lactylated were found be involved several biological processes, including-but not limited to-amino acid metabolism, ribosomal protein synthesis, fatty metabolism. In addition, numerous highly valuable lactate-modified from literature. Among them, verified lactate levels following two tumor-related obtained similar results: USP14 ABCF1. These will further investigated our future studies. This paper is lactylome it provides reliable foundation for research Kla

Язык: Английский

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Tumor cells impair immunological synapse formation via central nervous system-enriched metabolite

Cancer Cell, Год журнала: 2024, Номер 42(6), С. 985 - 1002.e18

Опубликована: Май 30, 2024

Язык: Английский

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Insights into the biochemical and biophysical mechanisms mediating the longevity of the transparent optics of the eye lens

Journal of Biological Chemistry, Год журнала: 2022, Номер 298(11), С. 102537 - 102537

Опубликована: Сен. 27, 2022

A summary of key factors needed in the development and maintenance transparency optical properties aging lens is seen Figure 8. Interactions at molecular cellular levels account for formation transparent symmetric optics that contribute to refractive living "refracton" eye. Their significance visual function cannot be overstated. From perspective global health, these can impact progress on novel therapeutics preserve improve vision, specifically populations. As a challenging scientific problem, biology interactions between light waves organic matter basis extracellular tissues. Systematic studies are providing new knowledge about membrane, cytoskeletal, cytoplasmic adaptations, which generate image-forming refracton how it maintained matures over lifetime. The signaling mechanisms synchronize proliferation, migration, elongation, as highly optically tissue unique lens. valuable model study both longevity. This particularly true with respect protein stabilization involving PTMs, because very long-lived proteins not replaced other nontransparent tissues.Figure 8Key systematic review recent past advances cataract research provides insight into biochemical biophysical control short-range order (SRO), transparency, symmetry during aging. Note: While image largely index, linked closely protein, structure, supported by microcirculation, metabolism, biochemistry. These regulate cell elongation differentiation prolong longevity molecules cells isolated within capsule, thickest basement membrane any mammalian (102Nielsen J. Hedeholm R.B. Heinemeier Bushnell P.G. Christiansen J.S. Olsen et al.Eye radiocarbon reveals centuries Greenland shark (Somniosus microcephalus).Science. 2016; 353: 702-704Crossref PubMed Scopus (171) Google Scholar, 104Uwineza A. Kalligeraki A.A. Hamada N. Jarrin M. Quinlan R.A. Cataractogenic load - concept contribution ionizing radiation accelerated eye lens.Mutat. Res. 2019; 779: 68-81Crossref (29) 124Song S. Landsbury Dahm R. Liu Y. Zhang Q. Functions intermediate filament cytoskeleton lens.J. Clin. Invest. 2009; 119: 1837-1848Crossref (123) 184Fujii Takemoto L.J. Momose Matsumoto Hiroki K. Akaboshi Formation four isomers asp-151 residue aged human alphaA-crystallin natural aging.Biochem. Biophys. Commun. 1999; 265: 746-751Crossref (0) 290Pierscionek B.K. Regini J.W. gradient index eye: an opto-biological synchrony.Prog. Retin. Eye 2012; 31: 332-349Crossref (47) 342Subczynski W.K. Widomska Mainali L. Factors determining oxygen permeability biological membranes: transport across fiber-cell plasma membranes.Adv. Exp. Med. Biol. 2017; 977: 27-34Crossref (8) 423Patterson Characterization equatorial current lens.Ophthalmic 1988; 20: 139-142Crossref (14) 424Wolf L.V. Yang Wang Xie Braunger B. Tamm E.R. al.Identification pax6-dependent gene regulatory networks mouse lens.PLoS One. 4: e4159Crossref Scholar). Individual panels taken or adapted from Refs. (104Uwineza 131Masters P.M. Bada J.L. Zigler Jr., Aspartic acid racemization heavy weight crystallins water insoluble normal lenses cataracts.Proc. Natl. Acad. Sci. U. 1978; 75: 1204-1208Crossref 425Braakhuis A.J. Donaldson C.I. Lim J.C. P.J. Nutritional strategies prevent cataract: status future strategies.Nutrients. 11: 1186Crossref (38) 426Maisel H.C. Harding C.V. Alcala J.R. Kuszak Bradley Morphology Lens Molecular Cellular Biology Lens..in: Bloemendal H. Wiley Sons, New York1981Google Scholar); https://commons.wikimedia.org/wiki/File:Greenland_shark_profile.jpg). DF, differentiating fiber cell; MF, differentiated mature cells.View Large Image ViewerDownload Hi-res Download (PPT)

Язык: Английский

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Scaffold, mechanics and functions of nuclear lamins

FEBS Letters, Год журнала: 2023, Номер 597(22), С. 2791 - 2805

Опубликована: Окт. 10, 2023

Nuclear lamins are type-V intermediate filaments that involved in many nuclear processes. In mammals, A- and B-type assemble into separate physical meshwork underneath the inner membrane, lamina, with some residual fraction localized within nucleoplasm. Lamins major part of nucleoskeleton, providing mechanical strength flexibility to protect genome allow deformability, while also contributing gene regulation via interactions chromatin. While evolutionary ancestors all filament family proteins, their ultimate filamentous assembly is markedly different from cytoplasmic counterparts. Interestingly, hundreds genetic mutations lamina proteins have been causally linked a broad range human pathologies, termed laminopathies. These include muscular, neurological metabolic disorders, as well premature aging diseases. Recent technological advances contributed resolving structure corresponding organization. this review, we revisit multiscale lamin organization discuss its implications on mechanics chromatin lamina-associated domains.

Язык: Английский

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Chromatin plasticity in mechanotransduction

Current Opinion in Cell Biology, Год журнала: 2024, Номер 88, С. 102376 - 102376

Опубликована: Май 28, 2024

Living organisms can detect and respond to physical forces at the cellular level. The pathways that transmit these nucleus allow cells react quickly consistently environmental changes. Mechanobiology involves interaction between biological processes is crucial for driving embryonic development adapting cues during adulthood. Molecular studies have shown sense mechanical signals directly through membrane receptors linked cytoskeleton or indirectly biochemical cascades influence gene expression adaptation. This review will explore role of epigenetic modifications, emphasizing 3D genome architecture nuclear structures as responders stimuli, which ensure memory adaptability. Understanding how are transduced regulate cell functioning, governing such programming reprogramming, essential advancing our knowledge human diseases.

Язык: Английский

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The nexus of nuclear envelope dynamics, circular economy and cancer cell pathophysiology

European Journal of Cell Biology, Год журнала: 2024, Номер 103(2), С. 151394 - 151394

Опубликована: Фев. 6, 2024

The nuclear envelope (NE) is a critical component in maintaining the function and structure of eukaryotic nucleus. NE lamina are disassembled during each cell cycle to enable an open mitosis. Nuclear architecture construction deconstruction prime example circular economy, as it fulfills highly efficient recycling program bound continuous assessment quality functionality building blocks. Alterations dynamics have emerged important contributors both oncogenic transformation cancer progression. However, knowledge breakdown reassembly still limited fraction participating proteins complexes. As cells contain diverse nuclei terms DNA content, but also number, size, shape, great interest understand intricate relationship between these features pathophysiology. In this review, we provide insights into how those regulated, destabilization processes may alter economy. Moreover, expand lamina-associated domain region by using strategic algorithms, including Artificial Intelligence, infer protein associations, assess their location, predict cancer-type specificity with implications for future diagnosis, prognosis treatment. Using approach identified NUP98 MECP2 potential that exhibit upregulation Acute Myeloid Leukemia (LAML) patients early diagnosis.

Язык: Английский

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Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 12, 2024

Язык: Английский

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Nuclear Softness Promotes the Metastatic Potential of Large-Nucleated Colorectal Cancer Cells via the ErbB4-Akt1-Lamin A/C Signaling Pathway

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(7), С. 2748 - 2762

Опубликована: Янв. 1, 2024

Abnormal nuclear enlargement is a diagnostic and physical hallmark of malignant tumors.Large nuclei are positively associated with an increased risk developing metastasis; however, large nucleus inevitably more resistant to cell migration due its size.The present study demonstrated that the size primary colorectal cancer (CRC) cells at advanced stage was larger than early stage.In addition, CRC liver metastases were those corresponding tissues.CRC sorted into large-nucleated (LNCs) small-nucleated (SNCs).Purified LNCs exhibited greater constricted migratory metastatic capacity SNCs in vitro vivo.Mechanistically, ErbB4 highly expressed LNCs, which phosphorylated lamin A/C serine 22 via ErbB4-Akt1 signaling pathway.Furthermore, level negative determinant stiffness.Taken together, possessed potential ErbB4-Akt1-mediated phosphorylation softening.These results may provide treatment strategy for tumor metastasis by targeting stiffness patients cancer, particularly CRC.

Язык: Английский

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Intermediate filaments at a glance

Journal of Cell Science, Год журнала: 2024, Номер 137(16)

Опубликована: Авг. 15, 2024

Intermediate filaments (IFs) comprise a large family of versatile cytoskeletal proteins, divided into six subtypes with tissue-specific expression patterns. IFs have wide repertoire cellular functions, including providing structural support to cells, as well active roles in mechanical and signaling pathways. Consequently, defects are associated more than 100 diseases. In this Cell Science at Glance article, we discuss the established classes their general features, functions beyond support, recent advances field. We also highlight involvement disease potential use clinical markers pathological conditions. Finally, provide our view on current knowledge gaps future directions IF

Язык: Английский

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Phosphorylation of Lamin A/C regulates structural integrity of the nuclear envelope

Journal of Biological Chemistry, Год журнала: 2024, Номер 301(1), С. 108033 - 108033

Опубликована: Ноя. 28, 2024

Dynamic disassembly and reconstruction of the nuclear lamina during entry exit mitosis, respectively, are pivotal steps in proliferation higher eukaryotic cells. Although numerous post-translational modifications lamin proteins have been identified, key factors driving dynamics remain elusive. Here we identified CDK1-elicited phosphorylation sites on endogenous Lamin A/C characterized their functions regulation lamina. Specifically, mass spectrometry revealed CDK1-mediated at N-terminal Thr19/Ser22 C-terminal Ser390/Ser392 mitosis. Importantly, phospho-mimicking 4D mutant T19D/S22D/S390D/S392D completely disrupted A filamentous structure interphase Conversely, non-phosphorylatable T19A/S22A especially 4A T19A/S22A/S390A/S392A protected from depolymerization These results suggest that dephosphorylation both N- regulate dynamics. Engineering into LMNA gene resulted abnormalities micronucleus formation telophase. Perturbation is shown to prevent proper envelope impair integrity. findings reveal a previously undefined link between dynamics, plasticity, genomic stability cell cycle.

Язык: Английский

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