Protein damage, repair and proteolysis

Chondrogianni, Niki; Petropoulos, Isabelle; Grimm, Stefanie; Georgila, Konstantina; Karademir, Betül; Friguet, Bertrand; Grune, Tilman; Gonos, Efstathios S.

doi:10.1016/j.mam.2012.09.001

Cited by 209 publications

(175 citation statements)

References 1,008 publications

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“…The ubiquitination-dependent protein degradation may be mediated by either proteasome or lysosome. 30,31 Although both pathways have been reported in the regulation of gp130, 29 CD9 is required for the gp130-mediated BMX-STAT3 signaling in GSCs. Because CD9 binds to gp130 and stabilizes gp130 protein in GSCs, we next investigated whether CD9 regulates the downstream signaling of gp130 in GSCs.…”

Section: Resultsmentioning

confidence: 99%

Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells

et al. 2016

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Glioblastoma (GBM) is the most malignant and lethal brain tumor harboring glioma stem cells (GSCs) that promote tumor propagation and therapeutic resistance. GSCs preferentially express several critical cell surface molecules that regulate the prosurvival signaling for maintaining the stem cell-like phenotype. Tetraspanin CD9 has recently been reported as a GSC biomarker that is relevant to the GSC maintenance. However, the underlying molecular mechanisms of CD9 in maintaining GSC property remain elusive. Herein, we report that CD9 stabilizes the IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitindependent lysosomal degradation to facilitate the STAT3 activation in GSCs. CD9 is preferentially expressed in GSCs of human GBM tumors. Mass spectrometry analysis identified gp130 as an interacting protein of CD9 in GSCs, which was confirmed by immunoprecipitation and immunofluorescent analyses. Disrupting CD9 or gp130 by shRNA significantly inhibited the self-renewal and promoted the differentiation of GSCs. Moreover, CD9 disruption markedly reduced gp130 protein levels and STAT3 activating phosphorylation in GSCs. CD9 stabilized gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote the BMX-STAT3 signaling in GSCs. Importantly, targeting CD9 potently inhibited GSC tumor growth in vivo, while ectopic expression of the constitutively activated STAT3 (STAT3-C) restored the tumor growth impaired by CD9 disruption. Collectively, we uncovered a critical regulatory mechanism mediated by tetraspanin CD9 to maintain the stem cell-like property and tumorigenic potential of GSCs.

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Section: Resultsmentioning

confidence: 99%

Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells

et al. 2016

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“…Many NEPTMs occur during the biological life of proteins, leading to protein molecular aging. These chemical reactions interfere with normal functions by disrupting molecular conformations, altering enzymatic activities, reducing degradation capacities, or interfering with receptor recognitions (4,36). Among them, glycoxidation has been well-described, and its major contribution to the development of pathophysiological complications of various diseases, such as diabetes mellitus, has been established (37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Protein carbamylation is a hallmark of aging

Gorisse

Piètrement

Vuiblet

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

164

125

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Aging is a progressive process determined by genetic and acquired factors. Among the latter are the chemical reactions referred to as nonenzymatic posttranslational modifications (NEPTMs), such as glycoxidation, which are responsible for protein molecular aging. Carbamylation is a more recently described NEPTM that is caused by the nonenzymatic binding of isocyanate derived from urea dissociation or myeloperoxidase-mediated catabolism of thiocyanate to free amino groups of proteins. This modification is considered an adverse reaction, because it induces alterations of protein and cell properties. It has been shown that carbamylated proteins increase in plasma and tissues during chronic kidney disease and are associated with deleterious clinical outcomes, but nothing is known to date about tissue protein carbamylation during aging. To address this issue, we evaluated homocitrulline rate, the most characteristic carbamylation-derived product (CDP), over time in skin of mammalian species with different life expectancies. Our results show that carbamylation occurs throughout the whole lifespan and leads to tissue accumulation of carbamylated proteins. Because of their remarkably long half-life, matrix proteins, like type I collagen and elastin, are preferential targets. Interestingly, the accumulation rate of CDPs is inversely correlated with longevity, suggesting the occurrence of still unidentified protective mechanisms. In addition, homocitrulline accumulates more intensely than carboxymethyl-lysine, one of the major advanced glycation end products, suggesting the prominent role of carbamylation over glycoxidation reactions in age-related tissue alterations. Thus, protein carbamylation may be considered a hallmark of aging in mammalian species that may significantly contribute in the structural and functional tissue damages encountered during aging.

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“…In a previous study, Tatrai et al (2001) observed toxicity is the production of reactive oxygen species which further aggravate the normal homeostasis of the cells thereby affecting the biochemical integrity (Dewanjee et al 2013, Souid et al 2013. However, cells have marked defense mechanism to overcome the production of oxidatively modified protein with an increased proteolysis (Chondrogianni et al 2014). This might be the possible reason for altered protein structure and concentration in the present study coinciding with earlier observations about Cd intoxicated liver tissue of rate by FT-IR analysis (Krishnakumar et al 2012).…”

Section: Discussionmentioning

confidence: 98%

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Khan¹,

Liu²,

Li³

et al. 2017

Turk. J. Fish. Aquat. Sci.

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Contamination of aquatic ecosystems with toxic metals such as Cd 2+ and Pb 2+ is a serious issue in the industrialized world, which can affect freshwater fish even at low concentrations. The aim of the present study was to investigate the effect of Cd 2+ and Pb 2+ alone or in combination on the biochemical constituents of liver and muscle in Crucian carp using Fourier Transform Infrared Spectroscopy (FT-IR). Results from the spectral analysis revealed significant decline in protein and increase in lipids in the two tissues with marked effect caused by the combined exposure of Cd 2+ and Pb 2+ . In case of liver, alteration in the intensity and band area at amide I resulted in a differential response of structural protein for the exposed groups. Furthermore, a decrease in the α-helix and alterations in the nucleic acids content was also observed in both liver and muscle of the exposed fish. Moreover, biochemical alterations in the vital tissue of freshwater fish due to toxic contaminants can be used as a marker of environmental pollution with the help of FT-IR spectroscopy.

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Protein damage, repair and proteolysis

Cited by 209 publications

References 1,008 publications

Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells

Tetraspanin CD9 stabilizes gp130 by preventing its ubiquitin-dependent lysosomal degradation to promote STAT3 activation in glioma stem cells

Protein carbamylation is a hallmark of aging

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