Molecular Mechanism of Centrosomal Protein 57 in centrosome regulation

 

Hui-Chun Cheng (鄭惠春)

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan,

 


Abstract:

Centrosomes organize the microtubule-based spindle apparatus through pericentriolar matrix (PCM). Errors in centrosome regulation result in centrosome amplification and chromosome missegregation. Centrosomal Protein 57 (Cep57) is a coiled-coil scaffolding protein at the inner core of the PCM and is involved in cell cycle-dependent centrosome regulation. However, molecular mechanisms of Cep57 function in centrosome regulation remain unclear. Here we used a combined approach to elucidate the molecular role and mechanisms of Cep57 in vitro and cells. Cep57 assembles microtubules through phase separation, which is regulated by downstream factors. In cells, blocking Cep57 phase separation leads to centrosome amplification. Our study provides a molecular foundation for understanding Cep57-mediated mosaic variegated aneuploidy (MVA) syndrome.

 

Keywords: centrosome, coiled-coil protein, microtubule, Cep57

 

References:

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[2] Watanabe K, Takao D, Ito KK, Takahashi M, Kitagawa D. The Cep57-pericentrin module organizes PCM expansion and centriole engagement. Nat Commun. 2019 Feb 25;10(1):931. doi: 10.1038/s41467-019-08862-2. PMID: 30804344; PMCID: PMC6389942.

[3] Snape K, Hanks S, Ruark E, Barros-Núñez P, Elliott A, Murray A, Lane AH, Shannon N, Callier P, Chitayat D, Clayton-Smith J, Fitzpatrick DR, Gisselsson D, Jacquemont S, Asakura-Hay K, Micale MA, Tolmie J, Turnpenny PD, Wright M, Douglas J, Rahman N. Mutations in CEP57 cause mosaic variegated aneuploidy syndrome. Nat Genet. 2011 Jun;43(6):527-9. doi: 10.1038/ng.822. Epub 2011 May 8. PMID: 21552266; PMCID: PMC3508359.

[4] Yeh et al., Molecular Mechanism of Centrosomal Protein 57 in centrosome regulation, unpublished.

 


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