The Ubiquitin Code in the Ubiquitin-Proteasome System and Autophagy

Kwon, Yong Tae; Ciechanover, Aaron

doi:10.1016/j.tibs.2017.09.002

Cited by 618 publications

(496 citation statements)

References 109 publications

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“…Intriguingly, aSyn and GCase form aprotein complex in solution at lysosomal pH 5.5, with K d in the mm range,w hich dissociates at pH 7.4. [144] Understanding its function is crucial for treatment of early onset autosomal recessive PD because the majority of cases are linked to mutations in the parkin gene (PRKN). [143] Parkin is an E3 ubiquitin ligase,i nvolved in the ubiquitin post-translational modification of substrate lysines in proteasomal and autophagic protein degradation pathways.…”

Section: Angewandte Chemiementioning

confidence: 99%

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

et al. 2019

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Dopamine (DA) is the most important catecholamine in the brain, as it is the most abundant and the precursor of other neurotransmitters. Degeneration of nigrostriatal neurons of substantia nigra pars compacta in Parkinson's disease represents the best‐studied link between DA neurotransmission and neuropathology. Catecholamines are reactive molecules that are handled through complex control and transport systems. Under normal conditions, small amounts of cytosolic DA are converted to neuromelanin in a stepwise process involving melanization of peptides and proteins. However, excessive cytosolic or extraneuronal DA can give rise to nonselective protein modifications. These reactions involve DA oxidation to quinone species and depend on the presence of redox‐active transition metal ions such as iron and copper. Other oxidized DA metabolites likely participate in post‐translational protein modification. Thus, protein–quinone modification is a heterogeneous process involving multiple DA‐derived residues that produce structural and conformational changes of proteins and can lead to aggregation and inactivation of the modified proteins.

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Section: Angewandte Chemiementioning

confidence: 99%

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

et al. 2019

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“…Seven lysine residues have been identified (K6, K11, K27, K29, K33, K48 and K63) on the ubiquitin molecule [2]. Also, additional Ub molecules can be attached onto one of the seven lysine residues or the N-terminal methionine to form polyubiquitin chains (polyUb) [2,3]. Perhaps, Ub is most well-known as the crucial marker of the Ubiquitin-Proteasome System (UPS), in which ubiquitinated proteins enter proteasomal degradation via 26S proteasome ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Regulatory interplay between deubiquitinating enzymes and cytokines

Woo

Baek

2019

Cytokine & Growth Factor Reviews

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A B S T R A C TDeubiquitinating enzymes (DUBs) are cysteine protease proteins that reverse the ubiquitination by removing ubiquitins from the target protein. With over 100 DUBs identified and categorized into at least 7 families, many DUBs interact with one or more cytokines, influencing cellular processes, such as antiviral responses, inflammatory responses, apoptosis, etc. While some DUBs influence cytokine pathway or production, some DUBs are cytokine-inducible. In this article, we summarize a list of DUBs, their interaction with cytokines, target proteins and mechanisms of action.

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“…Wenn allerdings nur ein Allel mutiert ist, findet man eine starke Assoziation mit der Parkinson-Krankheit. [144] Die Aufklärung seiner Funktion ist entscheidend fürd ie Behandlung der frühauftretenden autosomal-rezessiven PD,da die Mehrzahl der Fälle mit Mutationen im Parkin-Gen (PRKN)g ekoppelt ist. [138,139] Vork urzem konnte auch nachgewiesen werden, [140] dass die DA-Oxidation zu DAQe ine kovalente Modifikation der GCase am Cys-Rest im aktiven Zentrum verursacht, [141] was eine verringerte Enzymaktivität, eine Fehlfunktion der Lysosomen und eine Akkumulation von aSyn nach sich zieht.…”

Section: Dopaminmodifikation Von Proteinen Und Peptidenunclassified

Dopamin, oxidativer Stress und Protein‐Chinonmodifikationen bei Parkinson und anderen neurodegenerativen Erkrankungen

Monzani¹,

Nicolis²,

Dell’Acqua³

et al. 2019

Angewandte Chemie

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Dopamin (DA) ist das wichtigste und häufigste Catecholamin im Gehirn und zugleich Vorläufer anderer Neurotransmitter. Die Degeneration von Neuronen des Nigrostriatums (Substantia nigra, Pars compacta) bei Parkinson‐Kranken ist die am besten untersuchte Verknüpfung zwischen Neurotransmission und Neuropathologie durch DA. Catecholamine sind reaktive Moleküle, für die es komplexe Kontroll‐ und Transportsysteme gibt. Unter normalen Bedingungen werden kleine Mengen cytosolischen Dopamins unter Melanisierung von Peptiden und Proteinen schrittweise zu Neuromelanin umgewandelt. Überschießendes cytosolisches oder extraneuronales DA kann allerdings unselektive Proteinmodifikationen auslösen. Die dabei ablaufende Oxidation von DA zu Chinonverbindungen hängt von der Gegenwart redoxaktiver Übergangsmetallionen wie Eisen und Kupfer ab. Auch andere oxidierte DA‐Metaboliten sind wahrscheinlich an posttranslationalen Proteinmodifikationen beteiligt. Die Protein‐Chinonmodifikation ist also ein heterogener Vorgang mit verschiedenen DA‐Abkömmlingen, die Struktur‐ und Konformationsänderungen von Proteinen hervorrufen; dies kann zur Aggregation und Inaktivierung der modifizierten Proteine führen.

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The Ubiquitin Code in the Ubiquitin-Proteasome System and Autophagy

Cited by 618 publications

References 109 publications

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

Regulatory interplay between deubiquitinating enzymes and cytokines

Dopamin, oxidativer Stress und Protein‐Chinonmodifikationen bei Parkinson und anderen neurodegenerativen Erkrankungen

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