Proteasomes and their kin: proteases in the machine age

Pickart, Cecile M.; Cohen, Robert E.

doi:10.1038/nrm1336

Cited by 665 publications

(597 citation statements)

References 98 publications

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“…Furthermore, it shares functional and architectural features with other energy-dependent protease systems such as HslVU in prokaryotes and the 26S proteasome in eukaryotes (Bochtler et al, 1999;Pickart and Cohen, 2004;Rohrwild et al, 1996;Song et al, 2000;Yu and Houry, 2007). Structural and biochemical studies of these ATPdependent proteases have provided a wealth of information regarding the mechanism of substrate recognition and protease activation Lee et al, 2010a;Park and Song, 2008;Park et al, 2007;Rabl et al, 2008;Ramachandran et al, 2002;Song et al, 2000;Sousa et al, 2000;Wang et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

Lee

Kim

Song

2011

Molecules and Cells

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Section: Introductionmentioning

confidence: 99%

Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

Lee

Kim

Song

2011

Molecules and Cells

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“…The 26S proteasome consists of a 20S catalytic core, flanked by two 19S regulatory complexes. 5,6 The 20S catalytic core is composed of a total of 28 α-and β-type subunits, which are organized in a barrel with four stacked rings. The outer two rings are formed by seven α-type subunits each, the two inner rings by seven β-type subunits each.…”

mentioning

confidence: 99%

“…The outer two rings are formed by seven α-type subunits each, the two inner rings by seven β-type subunits each. 5 All α-and β-type subunits are needed for structural integrity of the proteasome. 7 Three β-type subunits, β1, β2 and β5, have proteolytic activity.…”

mentioning

confidence: 99%

“…6 The 19S regulatory particle is composed of at least 19 subunits involved in recognition of ubiquitin-conjugated substrates, ATP hydrolysis, de-ubiquitination, protein unfolding and feeding of the substrates into the 20S catalytic core for degradation. 5 Genetic studies in yeast and Drosophila have revealed that mutations in many subunits of the 20S core and the 19S regulatory domains impair proteasome function. 8,9 Genetic analysis of proteasome function is also of clinical importance as proteasome inhibition may be used as potential antitumor strategy, especially for treatment of multiple myeloma.…”

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confidence: 99%

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The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila

et al. 2016

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A major function of ubiquitylation is to deliver target proteins to the proteasome for degradation. In the apoptotic pathway in Drosophila, the inhibitor of apoptosis protein 1 (Diap1) regulates the activity of the initiator caspase Dronc (death regulator Nedd2-like caspase; caspase-9 ortholog) by ubiquitylation, supposedly targeting Dronc for degradation by the proteasome. Using a genetic approach, we show that Dronc protein fails to accumulate in epithelial cells with impaired proteasome function suggesting that it is not degraded by the proteasome, contrary to the expectation. Similarly, decreased autophagy, an alternative catabolic pathway, does not result in increased Dronc protein levels. However, combined impairment of the proteasome and autophagy triggers accumulation of Dronc protein levels suggesting that autophagy compensates for the loss of the proteasome with respect to Dronc turnover. Consistently, we show that loss of the proteasome enhances endogenous autophagy in epithelial cells. We propose that enhanced autophagy degrades Dronc if proteasome function is impaired.

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“…The UPS is a major cellular mechanism that regulates intracellular protein levels and eliminates damaged, misfolded and mutant proteins (Glickman & Ciechanover 2002). UPS substrates are covalently conjugated with ubiquitin (Ub), a highly conserved 76-residue protein, and polyubiquitinated proteins are mostly targeted to 26S proteasomes for proteolysis into small peptides of 3–24 amino acids (Pickart & Cohen 2004). MG132 is a potent, membrane-permeable proteasome inhibitor, which can inhibit proteasome activity and block the degradation of polyubiquitinated proteins (Lee & Goldberg 1998).…”

Section: Introductionmentioning

confidence: 99%

Proteasome inhibition attenuates rasfonin-induced autophagy concurring with the upregulation of caspase-dependent apoptosis

Yan

Che²,

Jiang

2016

Mycology

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Two major protein quality control mechanisms exist in eukaryotic cells, the ubiquitin-proteasome system (UPS) and the autophagy–lysosome system. Generally, the inhibition of UPS is believed to enhance autophagic pathway; nevertheless, the crosstalk between these two degradation systems may be much more complicated. Rasfonin, a 2-pyrone derivative of fungal secondary metabolites, is demonstrated to have the antitumor effect and can function as an autophagy inducer. Here, we reported that rasfonin activated multiple cell death pathways, including caspase-dependent apoptosis. Using electroscopy and microscopy, we observed rasfonin increased the formation of autophagosome. In immunoblotting assay, rasfonin enhanced autophagic flux concomitant with the upregulation of ubiquitination. MG132, an inhibitor of proteasome, attenuated rasfonin-dependent autophagy, whereas its presentation stimulated rasfonin-induced cleavage of poly (ADP-ribose) polymerase, a marker of caspase-dependent apoptosis. Together, we demonstrated that rasfonin induced the activation of both UPS and autophagic pathway, and the inhibition of UPS attenuated rasfonin-induced autophagy and enhanced the cytotoxicity of rasonin by upregulation of caspase-dependent apoptosis.

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Proteasomes and their kin: proteases in the machine age

Cited by 665 publications

References 98 publications

Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila

Proteasome inhibition attenuates rasfonin-induced autophagy concurring with the upregulation of caspase-dependent apoptosis

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