CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72

Zhenguang Ying, Kaifang Wang, Junfeng Wu, Mingyu Wang, Jing Yang, Xia Wang, Guowei Zhou, Haibin Chen, Hongwu Xu, Stephen Cho Wing Sze, Feng Gao, Chunman Li*, Ou Sha*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

1 Citation (Scopus)

Abstract

Background: The centrosome is one of the most important non-membranous organelles regulating microtubule organization and progression of cell mitosis. The coiled-coil alpha-helical rod protein 1 (CCHCR1, also known as HCR) gene is considered to be a psoriasis susceptibility gene, and the protein is suggested to be localized to the P-bodies and centrosomes in mammalian cells. However, the exact cellular function of HCR and its potential regulatory role in the centrosomes remain unexplored.

Results: We found that HCR interacts directly with astrin, a key factor in centrosome maturation and mitosis. Immunoprecipitation assays showed that the coiled-coil region present in the C-terminus of HCR and astrin respectively mediated the interaction between them. Astrin not only recruits HCR to the centrosome, but also protects HCR from ubiquitin-proteasome-mediated degradation. In addition, depletion of either HCR or astrin significantly reduced centrosome localization of CEP72 and subsequent MCPH proteins, including CEP152, CDK5RAP2, and CEP63. The absence of HCR also caused centriole duplication defects and mitotic errors, resulting in multipolar spindle formation, genomic instability, and DNA damage.

Conclusion: We conclude that HCR is localized and stabilized at the centrosome by directly binding to astrin. HCR are required for the centrosomal recruitment of MCPH proteins and centriolar duplication. Both HCR and astrin play key roles in keeping normal microtubule assembly and maintaining genomic stability.

Original languageEnglish
Article number240
Number of pages21
JournalBMC Biology
Volume20
Issue number1
Early online date24 Oct 2022
DOIs
Publication statusPublished - Dec 2022

Scopus Subject Areas

  • Biotechnology
  • Structural Biology
  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Plant Science
  • Developmental Biology
  • Cell Biology

User-Defined Keywords

  • Astrin
  • CCHCR1
  • Centrosome
  • CEP72
  • Microtubule organization
  • Mitosis

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