Oxidized proteins: Intracellular distribution and recognition by the proteasome

Jung, Tobias; Bader, Nicolle; Grune, Tilman

doi:10.1016/j.abb.2007.01.030

Cited by 71 publications

(51 citation statements)

References 81 publications

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“…This finding is in keeping with observation that NPM1 mutant protein might be susceptible to oxidative stress because of substitution of tryptophan 288 (W288) by cysteine at the C terminus of the protein. 17 Oxidized proteins might be the final target of proteasome machinery, 39 in accordance with what we have observed for NPM1 mutant degradation upon ATO and similarly to what reported for PML. 18 The antileukemic effect of ATO might be also because of PML NB targeting, which we show to happen upon ATO in NPM1-mutated AML cells, and has been reported as an event associated with p53 pathway activation leading to cell death.…”

Section: Discussionsupporting

confidence: 77%

Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells

Martelli

Gionfriddo

Mezzasoma

et al. 2015

Blood

122

116

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Key Points• ATRA and ATO affect NPM1 protein levels in AML cells and induce cell growth inhibition and apoptosis.• AML cells with mutated NPM1respond to ATRA/ATO, and this might be exploited therapeutically.Nucleophosmin (NPM1) mutations represent an attractive therapeutic target in acute myeloid leukemia (AML) because they are common (∼30% AML), stable, and behave as a founder genetic lesion. Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Adjunct of ATRA to chemotherapy was reported to be beneficial for NPM1-mutated AML patients. Leukemic cells with NPM1 mutation also showed sensibility to ATO in vitro. Here, we explore the mechanisms underlying these observations and show that ATO/ATRA induce proteasome-dependent degradation of NPM1 leukemic protein and apoptosis in NPM1-mutated AML cell lines and primary patients' cells. We also show that PML intracellular distribution is altered in NPM1-mutated AML cells and reverted by arsenic through oxidative stress induction. Interestingly, similarly to what was described for PML, oxidative stress also mediates ATO-induced degradation of the NPM1 mutant oncoprotein. Strikingly, NPM1 mutant downregulation by ATO/ATRA was shown to potentiate response to the anthracyclin daunorubicin. These findings provide experimental evidence for further exploring ATO/ATRA in preclinical NPM1-mutated AML in vivo models and a rationale for exploiting these compounds in chemotherapeutic regimens in clinics. (Blood. 2015;125(22):3455-3465)

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Section: Discussionsupporting

confidence: 77%

Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells

Martelli

Gionfriddo

Mezzasoma

et al. 2015

Blood

122

116

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“…This indicates that it follows the initial increase of ROS molecules and MDA levels. As a result of oxidative modification, proteins are being degraded by the proteasome complex, due to conformational changes and impaired function [26].…”

Section: Microwaves and Oxidative Stress In Testicular Tissuementioning

confidence: 99%

The Effects of Melatonin on Oxidative Stress Parameters and DNA Fragmentation in Testicular Tissue of Rats Exposed to Microwave Radiation

Djordjević¹,

Kocić²,

Stoimenov³

et al. 2015

Adv Clin Exp Med

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Background. Microwaves from mobile phones are one of the environmental toxicants that are capable of compromising male fertility by inducing oxidative stress and apoptosis in the testes. Melatonin is a lipophilic tryptophan indole amine and a potent antioxidant. Objectives. The aim of the study was to evaluate the effect of melatonin treatment on oxidative stress parameters and DNA fragmentation in the testicular tissue of rats exposed to microwave radiation (4 h/day). Material and Methods. Adult Wistar rats were divided in 4 groups: I -treated with saline; II -treated with melatonin; III -exposed to microwaves; IV -exposed to microwaves and treated with melatonin. The melatonin (2 mg/kg ip) was administered daily. The animals were sacrificed after 20, 40 and 60 days. Results. Melatonin treatment prevented previously registered increases in malondialdehyde after only 20 days. Furthermore, it reversed the effects of microwave exposure on xanthine oxidase (after 40 days) and acid-DNase activity (after 20 days). However, neither protein carbonyl content nor catalase and alkaline Dnase activity were changed due to melatonin treatment. Conclusions. Melatonin exerts potent antioxidant effects in the testes of rats exposed to microwaves by decreasing the intensity of oxidative stress; it also reduces DNA fragmentation (Adv Clin Exp Med 2015, 24, 3, 429-436).

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“…Proteins are one of the prime targets for oxidative damage (22), and cysteine residues are particularly sensitive to oxidation because the thiol group in cysteine can be oxidized to both reversible [sulfenic acid (SOH), disulfide bond formation (SOS)] and irreversible oxidative states [sulfinic (SO 2 H) and sulfonic acids (SO 3 H)] (23,24). Cysteine residues are important physiologically because they are often found at catalytic and regulatory sites in proteins and enzymes (24).…”

mentioning

confidence: 99%

Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat

Pérez¹,

Buffenstein

Masamsetti³

et al. 2009

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

370

347

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The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. Surprisingly, data from the longest-living rodent known, naked molerats [MRs; mass 35 g; maximum lifespan (MLSP) > 28.3 years], when compared with mice (MLSP 3.5 years) exhibit higher levels of lipid peroxidation, protein carbonylation, and DNA oxidative damage even at a young age. We hypothesize that age-related changes in protein structural stability, oxidation, and degradation are abrogated over the lifespan of the MR. We performed a comprehensive study of oxidation states of protein cysteines [both reversible (sulfenic, disulfide) and indirectly irreversible (sulfinic/sulfonic acids)] in liver from young and old C57BL/6 mice (6 and 28 months) and MRs (2 and >24 years). Furthermore, we compared interspecific differences in urea-induced protein unfolding and ubiquitination and proteasomal activity. Compared with data from young mice, young MRs have 1.6 times as much free protein thiol groups and similar amounts of reversible oxidative damage to cysteine. In addition, they show less urea-induced protein unfolding, less protein ubiquitination, and higher proteasome activity. Mice show a significant age-related increase in cysteine oxidation and higher levels of ubiquitination. In contrast, none of these parameters were significantly altered over 2 decades in MRs. Clearly MRs have markedly attenuated age-related accrual of oxidation damage to thiol groups and age-associated up-regulation of homeostatic proteolytic activity. These pivotal mechanistic interspecies differences may contribute to the divergent aging profiles and strongly implicate maintenance of protein stability and integrity in successful aging.cysteine oxidation ͉ Heterocephalus glaber ͉ mechanisms of aging ͉ proteasome activity ͉ protein homeostasis

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Oxidized proteins: Intracellular distribution and recognition by the proteasome

Cited by 71 publications

References 81 publications

Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells

Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells

The Effects of Melatonin on Oxidative Stress Parameters and DNA Fragmentation in Testicular Tissue of Rats Exposed to Microwave Radiation

Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat

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