ANKRD26 recruits PIDD1 to centriolar distal appendages to activate the PIDDosome following centrosome amplification

Lauren T. Evans, Taylor Anglen, Phillip Scott, Kimberly Lukasik, Jadranka Loncarek, Andrew J. Holland

Research output: Contribution to journalArticlepeer-review

Abstract

Centriole copy number is tightly maintained by the once-per-cycle duplication of these organelles. Centrioles constitute the core of centrosomes, which organize the microtubule cytoskeleton and form the poles of the mitotic spindle. Centrosome amplification is frequently observed in tumors, where it promotes aneuploidy and contributes to invasive phenotypes. In non-transformed cells, centrosome amplification triggers PIDDosome activation as a protective response to inhibit cell proliferation, but how extra centrosomes activate the PIDDosome remains unclear. Using a genome-wide screen, we identify centriole distal appendages as critical for PIDDosome activation in cells with extra centrosomes. The distal appendage protein ANKRD26 is found to interact with and recruit the PIDDosome component PIDD1 to centriole distal appendages, and this interaction is required for PIDDosome activation following centrosome amplification. Furthermore, a recurrent ANKRD26 mutation found in human tumors disrupts PIDD1 localization and PIDDosome activation in cells with extra centrosomes. Our data support a model in which ANKRD26 initiates a centriole-derived signal to limit cell proliferation in response to centrosome amplification.

Original languageEnglish (US)
JournalEMBO Journal
DOIs
StateAccepted/In press - 2020

Keywords

  • ANKRD26
  • centriole
  • centriole amplification
  • PIDDosome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'ANKRD26 recruits PIDD1 to centriolar distal appendages to activate the PIDDosome following centrosome amplification'. Together they form a unique fingerprint.

Cite this