ArticleInfection and immunity2007
Evading the proteasome: absence of lysine residues contributes to pertussis toxin activity by evasion of proteasome degradation.
Article in Infection and immunity, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 53 citations in OpenAlex.
- Novel PE-DT-fusion toxin enhances internalization and target-dependently restores the cytotoxicity of recombinant immunotoxins.Frontiers in pharmacology · 2026Article
- The antiarrhythmic drugs amiodarone and dronedarone inhibit intoxication of cells with pertussis toxin.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- ER-transiting bacterial toxins amplify STING innate immune responses and elicit ER stress.Infection and immunity · 2024Article
- The Chaperonin TRiC/CCT Inhibitor HSF1A Protects Cells from Intoxication with Pertussis Toxin.Toxins · 2024Article
- Domperidone InhibitsToxins · 2023Article
- Inhibition of Pertussis Toxin by Human α-Defensins-1 and -5: Differential Mechanisms of Action.International journal of molecular sciences · 2023Article
- Lysine deserts prevent adventitious ubiquitylation of ubiquitin-proteasome components.Cellular and molecular life sciences : CMLS · 2023Article
- Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Novel Strategies to Inhibit Pertussis Toxin.Toxins · 2022Review
- Non-lysine ubiquitylation: Doing things differently.Frontiers in molecular biosciences · 2022Review
- Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins.Frontiers in cellular and infection microbiology · 2022Review
- Reduced cytotoxicity by mutation of lysine 590 ofImmunotherapy advances · 2022Article
- Article
- Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo.Scientific reports · 2021Article
- Proline Isomerization as a Key Determinant for Hsp90-Toxin Interactions.Frontiers in cellular and infection microbiology · 2021Article
- Review
- Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process.International journal of molecular sciences · 2019Review
- Role of Major Toxin Virulence Factors in Pertussis Infection and Disease Pathogenesis.Advances in experimental medicine and biology · 2019Article
- Article
- Thermal Unfolding of the Pertussis Toxin S1 Subunit Facilitates Toxin Translocation to the Cytosol by the Mechanism of Endoplasmic Reticulum-Associated Degradation.Infection and immunity · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Pertussis toxin (PT) is an important virulence factor produced by Bordetella pertussis. PT holotoxin comprises one enzymatically active A subunit (S1), associated with a pentamer of B subunits. PT is an ADP-ribosyltransferase that modifies several mammalian heterotrimeric G proteins. Some bacterial toxins are believed to undergo retrograde intracellular transport through the Golgi apparatus to the endoplasmic reticulum (ER). The ER-associated degradation (ERAD) pathway involves the removal of misfolded proteins from the ER and degradation upon their return to the cytosol; this pathway may be exploited by PT and other toxins. In the cytosol, ERAD substrates are ubiquitinated at lysine residues, targeting them to the proteasome for degradation. We hypothesize that S1 avoids ubiquitination and proteasome degradation due to its lack of lysine residues. We predicted that the addition of lysine residues would reduce PT toxicity by allowing ubiquitination and degradation to occur. Variant forms of PT were engineered, replacing one, two, or three arginines with lysines in a variety of locations on S1. Several variants were identified with wild-type in vitro enzymatic activity but reduced cellular activity, consistent with our hypothesis. Significant recovery of the cellular activity of these variants was observed when CHO cells were pretreated with a proteasome inhibitor. We concluded that the replacement of arginine residues with lysine in the S1 subunit of PT renders the toxin subject to proteasomal degradation, suggesting that wild-type PT avoids proteasome degradation due to an absence of lysine residues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.