Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome

By D. Finley. Annual Review of Biochemistry, 2009

1,766 citations recorded by the source corpus.

The proteasome is an intricate molecular machine, which serves to degrade proteins following their conjugation to ubiquitin. Substrates dock onto the proteasome at its 19-subunit regulatory particle via a diverse set of ubiquitin receptors, and are then translocated into an internal chamber within the 28-subunit proteolytic core particle, where they are hydrolyzed. Substrate is threaded into the core particle through a narrow gated channel, and thus translocation requires ATP-dependent unfolding of the substrate. Six distinct ATPases in the regulatory particle appear to form a ring complex and to drive unfolding as well as translocation. ATP-dependent, degradation-coupled deubiquitination of the substrate is required both for efficient substrate degradation and for suppressing ubiquitin degradation. However, the proteasome also contains deubiquitinating enzymes that act on substrates prior to degradation, thus suppressing substrate degradation. Here we examine the key elements of this molecular machine and how they cooperate in the processing of proteolytic substrates.

Subfields: Epidemiology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/d53890b192720067ceb72affd49cd37815b25c37

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In Epidemiology

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Citations in the corpus

• The Logic of the 26S Proteasome. (2017, neutral): “However, it is now clear that ubiquitylation and even the association of a ubiquitylated protein with the proteasome do not necessarily lead to its degradation (Finley, 2009; Inobe and Matouschek, 2014).”
• ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now? (2019, background): “In the UPS pathway, proteins are marked for degradation by ubiquitination before being recognized and degraded by the proteasome (Finley, 2009).”
• Complete subunit architecture of the proteasome regulatory particle (2012, neutral): “The proteasome thus controls a myriad of essential cellular processes, including the cell cycle, transcription and protein quality contro”
• The N‐end rule pathway and regulation by proteolysis (2011, background): “The term ‘‘Ub ligase’’ denotes either an E2-E3 complex or its E3 component.(6,54,57,62) In eukaryotes, the N-end rule pathway comprises two major branches, one of which is termed the Arg/N-end rule pathway.”
• The ubiquitin code. (2012, background): “The degradation of plasma membrane proteins occurs in lysosomes, and substrates are targeted to this proteolytic compartment chains (140).”