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  • Knyazeva, Anastasia,1995-Umeå universitet,Kemiska institutionen,Umeå Centre for Microbial Research (UCMR),Science for Life Laboratory, Umeå University, Umeå, Sweden (author)

A chemical inhibitor of IST1-CHMP1B interaction impairs endosomal recycling and induces noncanonical LC3 lipidation

  • Article/chapterEnglish2024

Publisher, publication year, extent ...

  • Proceedings of the National Academy of Sciences,2024
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-225949
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-225949URI
  • https://doi.org/10.1073/pnas.2317680121DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The endosomal sorting complex required for transport (ESCRT) machinery constitutes multisubunit protein complexes that play an essential role in membrane remodeling and trafficking. ESCRTs regulate a wide array of cellular processes, including cytokinetic abscission, cargo sorting into multivesicular bodies (MVBs), membrane repair, and autophagy. Given the versatile functionality of ESCRTs, and the intricate organizational structure of the ESCRT machinery, the targeted modulation of distinct ESCRT complexes is considerably challenging. This study presents a pseudonatural product targeting IST1-CHMP1B within the ESCRT-III complexes. The compound specifically disrupts the interaction between IST1 and CHMP1B, thereby inhibiting the formation of IST1-CHMP1B copolymers essential for normal-topology membrane scission events. While the compound has no impact on cytokinesis, MVB sorting, or biogenesis of extracellular vesicles, it rapidly inhibits transferrin receptor recycling in cells, resulting in the accumulation of transferrin in stalled sorting endosomes. Stalled endosomes become decorated by lipidated LC3, suggesting a link between noncanonical LC3 lipidation and inhibition of the IST1-CHMP1B complex.

Subject headings and genre

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  • Li, ShuangUmeå universitet,Kemiska institutionen,Umeå Centre for Microbial Research (UCMR),Science for Life Laboratory, Umeå University, Umeå, Sweden(Swepub:umu)shac0003 (author)
  • Corkery, Dale P.Umeå universitet,Kemiska institutionen,Umeå Centre for Microbial Research (UCMR),Science for Life Laboratory, Umeå University, Umeå, Sweden(Swepub:umu)daco0023 (author)
  • Shankar, KasturikaUmeå universitet,Umeå Centre for Microbial Research (UCMR),Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för medicinsk kemi och biofysik(Swepub:umu)kash0020 (author)
  • Herzog, Laura K.Umeå universitet,Umeå Centre for Microbial Research (UCMR),Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Molekylär Infektionsmedicin, Sverige (MIMS)(Swepub:umu)lahe0084 (author)
  • Zhang, XuepeiChemical Proteomics Core Facility, Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Chemical Proteomics Unit, Science for Life Laboratory, Stockholm, Sweden; Chemical Proteomics, Swedish National Infrastructure for Biological Mass Spectrometry, Stockholm, Sweden (author)
  • Singh, BirendraUmeå universitet,Anestesiologi och intensivvård(Swepub:umu)bisi0005 (author)
  • Niggemeyer, GeorgDepartment of Chemical Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany (author)
  • Grill, DavidDepartment of Chemical Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany (author)
  • Gilthorpe, Jonathan D.Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)(Swepub:umu)jogi0002 (author)
  • Gaetani, MassimilianoChemical Proteomics Core Facility, Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Chemical Proteomics Unit, Science for Life Laboratory, Stockholm, Sweden; Chemical Proteomics, Swedish National Infrastructure for Biological Mass Spectrometry, Stockholm, Sweden (author)
  • Carlson, Lars-AndersUmeå universitet,Umeå Centre for Microbial Research (UCMR),Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för medicinsk kemi och biofysik(Swepub:umu)laca0012 (author)
  • Waldmann, HerbertDepartment of Chemical Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany; Faculty of Chemistry and Chemical Biology, Technical University Dortmund, Dortmund, Germany (author)
  • Wu, Yao-Wen,ProfessorUmeå universitet,Kemiska institutionen,Umeå Centre for Microbial Research (UCMR),Science for Life Laboratory, Umeå University, Umeå, Sweden(Swepub:umu)yawu0006 (author)
  • Umeå universitetKemiska institutionen (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences121:170027-84241091-6490

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