Bacterial Proteasomes: Mechanistic and Functional Insights

Becker, Samuel H.; Darwin, K. Heran

doi:10.1128/mmbr.00036-16

Cited by 47 publications

(40 citation statements)

References 120 publications

(226 reference statements)

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“…While the protozoan proteasome is an unusual drug target, even more surprising is the use of proteasome inhibitors as antibiotics. Although the proteasome is essential in eukaryotes, there are conditionally essential proteasomal genes in many bacterial Actinomycetales and Nitrospirales lineages [239]. This includes highly pathogenic species Mycobacterium tuberculosis, a major global threat affecting at least 10 million people in 2017 [240][241][242][243][244].…”

Section: Other Indications For Proteasome Inhibitorsmentioning

confidence: 99%

Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease

Sherman

Li²

2020

Molecules

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The proteasome is the central component of the main cellular protein degradation pathway. During the past four decades, the critical function of the proteasome in numerous physiological processes has been revealed, and proteasome activity has been linked to various human diseases. The proteasome prevents the accumulation of misfolded proteins, controls the cell cycle, and regulates the immune response, to name a few important roles for this macromolecular “machine.” As a therapeutic target, proteasome inhibitors have been approved for the treatment of multiple myeloma and mantle cell lymphoma. However, inability to sufficiently inhibit proteasome activity at tolerated doses has hampered efforts to expand the scope of proteasome inhibitor-based therapies. With emerging new modalities in myeloma, it might seem challenging to develop additional proteasome-based therapies. However, the constant development of new applications for proteasome inhibitors and deeper insights into the intricacies of protein homeostasis suggest that proteasome inhibitors might have novel therapeutic applications. Herein, we summarize the latest advances in proteasome inhibitor development and discuss the future of proteasome inhibitors and other proteasome-based therapies in combating human diseases.

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Section: Other Indications For Proteasome Inhibitorsmentioning

confidence: 99%

Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease

Sherman

Li²

2020

Molecules

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“…Entoporibacteria and Pelagiporibacteria genomes both contain a large number of factors typically linked to a eukaryotic host-associated lifestyle. These include enhanced adhesion to eukaryotic cell surfaces; digestion of host tissue via heparinases [90], neuraminidases [91], ceramidases [92], and chitinases [93]; the incorporation of phosphoinositol-linked glycolipids into cell membranes [94]; the formation of exopolysaccharide capsules containing host cell surface-mimicking domains [85,95]; the production of mycothiol to undermine oxidative host defenses [72]; and the targeting of pupylated substrates to bacterial proteosomes, previously shown to be a mechanism for inactivating lysosomal enzymes after engulfment by host macrophages [96]. The suggestion that much of the sinking particulate matter in the open ocean originates from marine eukaryotic hosts [84], offers an intriguing possible explanation for the unexpected abundance of functional activities characteristic of host association in Pelagiporibacteria genomes.…”

Section: Potential Environmental Adaptationsmentioning

confidence: 99%

Pangenomic comparison of globally distributed Poribacteria associated with sponge hosts and marine particles

et al. 2018

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Candidatus Poribacteria is a little-known bacterial phylum, previously characterized by partial genomes from a single sponge host, but never isolated in culture. We have reconstructed multiple genome sequences from four different sponge genera and compared them to recently reported, uncharacterized Poribacteria genomes from the open ocean, discovering shared and unique functional characteristics. Two distinct, habitat-linked taxonomic lineages were identified, designated Entoporibacteria (sponge-associated) and Pelagiporibacteria (free-living). These lineages differed in flagellar motility and chemotaxis genes unique to Pelagiporibacteria, and highly expanded families of restriction endonucleases, DNA methylases, transposases, CRISPR repeats, and toxin-antitoxin gene pairs in Entoporibacteria. Both lineages shared pathways for facultative anaerobic metabolism, denitrification, fermentation, organosulfur compound utilization, type IV pili, cellulosomes, and bacterial proteosomes. Unexpectedly, many features characteristic of eukaryotic host association were also shared, including genes encoding the synthesis of eukaryotic-like cell adhesion molecules, extracellular matrix digestive enzymes, phosphoinositol-linked membrane glycolipids, and exopolysaccharide capsules. Complete Poribacteria 16S rRNA gene sequences were found to contain multiple mismatches to "universal" 16S rRNA gene primer sets, substantiating concerns about potential amplification failures in previous studies. A newly designed primer set corrects these mismatches, enabling more accurate assessment of Poribacteria abundance in diverse marine habitats where it may have previously been overlooked.

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“…Protein degradation in bacteria is mediated by several processes 24 . One of them is the so called transfer-messenger RNA (tmRNA) system, based on special RNA molecules that function both as tRNAs and mRNAs.…”

Section: Introductionmentioning

confidence: 99%