E3 ubiquitin ligase RNF123-deficient mice exhibit reduced parasitemia and mortality in rodent malaria (Plasmodium yoelii 17XL) infection

Miyasaka, Yuki; Niwa, Shota; Masuya, Tomomi; Ishii, Reika; Kobayashi, Misato; Horio, Fumihiko; Ohno, Tamio

doi:10.1016/j.parint.2022.102542

Cited by 2 publications

(3 citation statements)

References 26 publications

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“…Studies devoted to discovering new E3 ligase candidates both in the host and in the pathogen will advance PROTAC modality also in antiparasitic drug discovery. For instance, in 2022, the role of the host E3 ligase RNF123 in a rodent malaria infection has been disclosed . Another study found the host E3 ligase MARCH1 involved in the regulation of antimalarial immunity .…”

Section: Tpd Technologies In Parasitic Diseasesmentioning

confidence: 99%

“…For instance, in 2022, the role of the host E3 ligase RNF123 in a rodent malaria infection has been disclosed. 100 Another study found the host E3 ligase MARCH1 involved in the regulation of antimalarial immunity. 101 Additionally, in 2020, 28 enzymes belonging to the ubiquitin system of Leishmania proteasome have been described, and the UBC2-UEV1 E2 complex appeared to be implicated in differentiation processes.…”

Section: Tpd Technologies In Parasitic Diseasesmentioning

confidence: 99%

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Targeted Protein Degradation for Infectious Diseases: from Basic Biology to Drug Discovery

Chávez

Salerno

Liuzzi

et al. 2022

ACS Bio Med Chem Au

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Targeted protein degradation (TPD) is emerging as one of the most innovative strategies to tackle infectious diseases. Particularly, proteolysis-targeting chimera (PROTAC)-mediated protein degradation may offer several benefits over classical anti-infective small-molecule drugs. Because of their peculiar and catalytic mechanism of action, antiinfective PROTACs might be advantageous in terms of efficacy, toxicity, and selectivity. Importantly, PROTACs may also overcome the emergence of antimicrobial resistance. Furthermore, anti-infective PROTACs might have the potential to (i) modulate "undruggable" targets, (ii) "recycle" inhibitors from classical drug discovery approaches, and (iii) open new scenarios for combination therapies. Here, we try to address these points by discussing selected case studies of antiviral PROTACs and the first-in-class antibacterial PROTACs. Finally, we discuss how the field of PROTAC-mediated TPD might be exploited in parasitic diseases. Since no antiparasitic PROTAC has been reported yet, we also describe the parasite proteasome system. While in its infancy and with many challenges ahead, we hope that PROTAC-mediated protein degradation for infectious diseases may lead to the development of next-generation anti-infective drugs.

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Section: Tpd Technologies In Parasitic Diseasesmentioning

confidence: 99%

Section: Tpd Technologies In Parasitic Diseasesmentioning

confidence: 99%

Targeted Protein Degradation for Infectious Diseases: from Basic Biology to Drug Discovery

Chávez

Salerno

Liuzzi

et al. 2022

ACS Bio Med Chem Au

View full text Add to dashboard Cite

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“…Rodent malarial parasite infections were performed as described previously [10,11]. Red blood cells infected with the rodent malarial parasite, Plasmodium yoelii 17XL (P. yoelii 17XL), were stored as frozen stocks at −80 °C.…”

Section: Rodent Malaria Infectionsmentioning

confidence: 99%

A novel ENU-induced <i>Cpox</i> mutation causes microcytic hypochromic anemia in mice

et al. 2022

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Mouse models of red blood cell abnormalities are important for understanding the underlying molecular mechanisms of human erythrocytic diseases. DBA.B6-Mha (Microcytic hypochromic anemia) congenic mice were generated from the cross between N-ethyl-N-nitrosourea (ENU)-mutagenized male C57BL/6J and female DBA/2J mice as part of the RIKEN large-scale ENU mutagenesis project. The mice were established by backcrossing with DBA/2J mice for more than 20 generations. These mice showed autosomal-dominant microcytic hypochromic anemia with decreased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels and increased red blood cell distribution width (RDW) and plasma ferritin levels. Linkage analysis indicated that the Mha locus was located within an interval of approximately 1.95-Mb between D16Nut1 (58.35 Mb) and D16Mit185 (60.30 Mb) on mouse chromosome 16. Mutation analysis revealed that DBA.B6-Mha mice had a point mutation (c.921-2A>G) at the acceptor site of intron 4 in the coproporphyrinogen oxidase (Cpox) gene, a heme-synthesizing gene. RT-PCR revealed that the Cpox mRNA in DBA.B6-Mha mice caused splicing errors. Our results suggest that microcytic hypochromic anemia in DBA.B6-Mha mice is owing to impaired heme synthesis caused by splice mutations in Cpox. Therefore, the DBA.B6-Mha mice may be used to elucidate the molecular mechanisms underlying microcytic hypochromic anemia caused by mutations in Cpox. Although low MCV levels are known to confer malarial resistance to the host, there were no marked changes in the susceptibility of DBA.B6-Mha mice to rodent malarial (Plasmodium yoelii 17XL) infection.

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E3 ubiquitin ligase RNF123-deficient mice exhibit reduced parasitemia and mortality in rodent malaria (Plasmodium yoelii 17XL) infection

Cited by 2 publications

References 26 publications

Targeted Protein Degradation for Infectious Diseases: from Basic Biology to Drug Discovery

Targeted Protein Degradation for Infectious Diseases: from Basic Biology to Drug Discovery

A novel ENU-induced <i>Cpox</i> mutation causes microcytic hypochromic anemia in mice

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