Hydrophobicity as the signal for selective degradation of hydroxyl radical-modified hemoglobin by the multicatalytic proteinase complex, proteasome

Pacifici, Robert E.; Kono, Yoshiko; Davies, Kelvin J.A.

doi:10.1016/s0021-9258(18)82272-4

Cited by 230 publications

(25 citation statements)

References 58 publications

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“…Nonnative or partially denatured soluble proteins are subjected to ubiquitination and/or proteasome-mediated degradation (Pacifici et al, 1993;Sadis et al, 1995;Michalek et al, 1996;Gilon et al, 1998;Laney and Hochstrasser, 1999). A similar scenario may prevail for T70 CFTR if the COOH-terminal tail is engaged in the structural stabilization of CFTR in the post-ER compartment.…”

Section: Deletion Of the Cooh-terminal Tail Structurally Destabilizes Cftrmentioning

confidence: 99%

Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments

Benharouga

Haardt

Kartner

et al. 2001

The Journal of Cell Biology

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Impaired biosynthetic processing of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel, constitutes the most common cause of CF. Recently, we have identified a distinct category of mutation, caused by premature stop codons and frameshift mutations, which manifests in diminished expression of COOH-terminally truncated CFTR at the cell surface. Although the biosynthetic processing and plasma membrane targeting of truncated CFTRs are preserved, the turnover of the complex-glycosylated mutant is sixfold faster than its wild-type (wt) counterpart. Destabilization of the truncated CFTR coincides with its enhanced susceptibility to proteasome-dependent degradation from post-Golgi compartments globally, and the plasma membrane specifically, determined by pulse–chase analysis in conjunction with cell surface biotinylation. Proteolytic cleavage of the full-length complex-glycosylated wt and degradation intermediates derived from both T70 and wt CFTR requires endolysosomal proteases. The enhanced protease sensitivity in vitro and the decreased thermostability of the complex-glycosylated T70 CFTR in vivo suggest that structural destabilization may account for the increased proteasome susceptibility and the short residence time at the cell surface. These in turn are responsible, at least in part, for the phenotypic manifestation of CF. We propose that the proteasome-ubiquitin pathway may be involved in the peripheral quality control of other, partially unfolded membrane proteins as well.

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Section: Deletion Of the Cooh-terminal Tail Structurally Destabilizes Cftrmentioning

confidence: 99%

Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments

Benharouga

Haardt

Kartner

et al. 2001

The Journal of Cell Biology

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“…This is probably due to the aggregation of MFP after strong oxidation treatment. After 6 days of incubation, the PDI significantly increased in MFP/OLA and MH-MFP/OLA, probably due to the dissociation or unfolding of MFP induced by oxidised linoleic acid during incubation (Pacifici et al, 1993). From the above results, we concluded that mildly oxidised MFP might lead to a cleavage of peptide backbones, which contributed to carbonyl generation and exposure of lysine residue (precursor of CML) in MFP.…”

Section: Sh and S-smentioning

confidence: 75%

“…In addition, it is worth noting that free amines increased significantly from 48.9 ± 3.81 nmol mg −1 (0 days) to 53.7 ± 1.04 nmol mg −1 (2 days) in MFP/OLA after 2 days of incubation (Figure 2A). Previous studies reported that hydroxyl radicals induced by oxidised linoleic acid subjected MFP to unfolding and degradation, which enhanced the exposure of amino acid residues, thereby increasing free amine content (Pacifici et al ., 1993). Therefore, it was reasonable that free amines significantly increased after 2 days of incubation.…”

Section: Resultsmentioning

confidence: 99%

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Effect of oxidation and hydrolysis of porcine myofibrillar protein on N^ε‐carboxymethyl‐lysine formation in model systems

Yu¹,

Zeng

et al. 2021

Int J of Food Sci Tech

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Summary This study investigated the effects of oxidation and hydrolysis of porcine myofibrillar protein (MFP) on Nε‐carboxymethyl‐lysine (CML) formation in model systems. Model systems of MFP/oxidised linoleic acid (MFP/OLA), mildly oxidised MFP/OLA (MO‐MFP/OLA), severely oxidised MFP/OLA (SO‐MFP/OLA), mildly hydrolysed MFP/OLA (MH‐MFP/OLA) and severely hydrolysed MFP/OLA (SH‐MFP/OLA) were incubated, and CML content was determined. Compared with MFP/OLA (39.1 ± 5.7 ng mg−1 protein), there was a significant increase of CML in MO‐MFP/OLA (53.9 ± 2.5 ng mg−1 protein), whereas a marked decrease was observed in SO‐MFP/OLA (25.1 ± 4.4 ng mg−1 protein) during incubation. CML level increased with increasing degree of hydrolysis of MFP after 6 days of incubation. Therefore, mildly oxidised MFP and hydrolysed MFP could promote CML formation, while severely oxidised MFP impeded CML generation. These results suggested that effects of oxidation and hydrolysis of MFP on CML generation were mainly dependent on the degree of structural changes of MFP.

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“…It is currently accepted that mild or moderate oxidative post-translational protein modifications lead to enhanced recognition and degradation by the 20S proteasome and that this constitutes a mechanism of removal and turnover of non-native proteins [ 24 , 36 , [43] , [44] , [45] , [46] ]. Indeed, amino acid oxidation usually leads to enhanced surface hydrophobicity and partial unfolding, characteristics that favor proteasome-dependent (and ATP-independent) protein degradation [ [47] , [48] , [49] , [50] ]. However, analysis of the precise effect of specific amino acid modifications is scarce in the literature and, in particular, there is a paucity of information on the specific impact of tyrosine nitration to 3-nitrotyrosine as a molecular feature for proteasome-dependent degradation.…”

Section: Discussionmentioning

confidence: 99%

Decreased proteasomal cleavage at nitrotyrosine sites in proteins and peptides

et al. 2021

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Removal of moderately oxidized proteins is mainly carried out by the proteasome, while highly modified proteins are no longer degradable. However, in the case of proteins modified by nitration of tyrosine residues to 3-nitrotyrosine (NO 2 Y), the role of the proteasome remains to be established. For this purpose, degradation assays and mass spectrometry analyses were performed using isolated proteasome and purified fractions of native cytochrome c (Cyt c ) and tyrosine nitrated proteoforms (NO 2 Y74-Cyt c and NO 2 Y97-Cyt c). While Cyt c treated under mild conditions with hydrogen peroxide was preferentially degraded by the proteasome, NO 2 Y74- and NO 2 Y97-Cyt c species did not show an increased degradation rate with respect to native Cyt c . Peptide mapping analysis confirmed a decreased chymotrypsin-like cleavage at C-terminal of NO 2 Y sites within the protein, with respect to unmodified Y residues. Additionally, studies with the proteasome substrate suc-LLVY-AMC (Y-AMC) and its NO 2 Y-containing analog, suc-LLVNO 2 Y-AMC (NO 2 Y-AMC) were performed, both using isolated 20S-proteasome and astrocytoma cell lysates as the proteasomal source. Comparisons of both substrates showed a significantly decreased proteasome activity towards NO 2 Y-AMC. Moreover, NO 2 Y-AMC, but not Y-AMC degradation rates, were largely diminished by increasing the reaction pH, suggesting an inhibitory influence of the additional negative charge contained in NO 2 Y-AMC secondary to nitration. The mechanism of slowing of proteasome activity in NO 2 Y-contaning peptides was further substantiated in studies using the phenylalanine and nitro-phenylalanine peptide analog substrates. Finally, degradation rates of Y-AMC and NO 2 Y-AMC with proteinase K were the same, demonstrating the selective inability of the proteasome to readily cleave at nitrotyrosine sites. Altogether, data indicate that the proteasome has a decreased capability to cleave at C-terminal of NO 2 Y residues in proteins with respect to the unmodified residues, making this a possible factor that decreases the turnover of oxidized proteins, if they are not unfolded, and facilitating the accumulation of nitrated proteins.

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Hydrophobicity as the signal for selective degradation of hydroxyl radical-modified hemoglobin by the multicatalytic proteinase complex, proteasome

Cited by 230 publications

References 58 publications

Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments

Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments

Effect of oxidation and hydrolysis of porcine myofibrillar protein on N^ε‐carboxymethyl‐lysine formation in model systems

Decreased proteasomal cleavage at nitrotyrosine sites in proteins and peptides

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Hydrophobicity as the signal for selective degradation of hydroxyl radical-modified hemoglobin by the multicatalytic proteinase complex, proteasome

Cited by 230 publications

References 58 publications

Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments

Cooh-Terminal Truncations Promote Proteasome-Dependent Degradation of Mature Cystic Fibrosis Transmembrane Conductance Regulator from Post-Golgi Compartments

Effect of oxidation and hydrolysis of porcine myofibrillar protein on Nε‐carboxymethyl‐lysine formation in model systems

Decreased proteasomal cleavage at nitrotyrosine sites in proteins and peptides

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Effect of oxidation and hydrolysis of porcine myofibrillar protein on N^ε‐carboxymethyl‐lysine formation in model systems