» Articles » PMID: 39195269

Centrosomal Protein 55 Regulates Chromosomal Instability in Cancer Cells by Controlling Microtubule Dynamics

Overview
Journal Cells
Publisher MDPI
Date 2024 Aug 28
PMID 39195269
Authors
Affiliations
Soon will be listed here.
Abstract

Centrosomal Protein 55 (CEP55) exhibits various oncogenic activities; it regulates the PI3K-Akt-pathway, midbody abscission, and chromosomal instability (CIN) in cancer cells. Here, we analyzed the mechanism of how CEP55 controls CIN in ovarian and breast cancer (OvCa) cells. Down-regulation of CEP55 reduced CIN in all cell lines analyzed, and CEP55 depletion decreased spindle microtubule (MT)-stability in OvCa cells. Moreover, recombinant CEP55 accelerated MT-polymerization and attenuated cold-induced MT-depolymerization. To analyze a potential relationship between CEP55-controlled CIN and its impact on MT-stability, we identified the CEP55 MT-binding peptides inside the CEP55 protein. Thereafter, a mutant with deficient MT-binding activity was re-expressed in CEP55-depleted OvCa cells and we could show that this mutant did not restore reduced CIN in CEP55-depleted cells. This finding strongly indicates that CEP55 regulates CIN by controlling MT dynamics.

Citing Articles

Mechanism of Centrosomal Protein 55 (CEP55) Loading Into Exosomes.

Dahlstroem C, Barezani J, Li J, Sopelniak K, Muhs S, Schneider C J Extracell Vesicles. 2025; 14(2):e70046.

PMID: 39976236 PMC: 11840697. DOI: 10.1002/jev2.70046.

References
1.
Huang Y, Jiang L, Yi Q, Lv L, Wang Z, Zhao X . Lagging chromosomes entrapped in micronuclei are not 'lost' by cells. Cell Res. 2012; 22(5):932-5. PMC: 3343657. DOI: 10.1038/cr.2012.26. View

2.
Windhorst S, Fliegert R, Blechner C, Mollmann K, Hosseini Z, Gunther T . Inositol 1,4,5-trisphosphate 3-kinase-A is a new cell motility-promoting protein that increases the metastatic potential of tumor cells by two functional activities. J Biol Chem. 2009; 285(8):5541-54. PMC: 2820782. DOI: 10.1074/jbc.M109.047050. View

3.
Jones D . Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol. 1999; 292(2):195-202. DOI: 10.1006/jmbi.1999.3091. View

4.
Ludwiczak J, Winski A, Szczepaniak K, Alva V, Dunin-Horkawicz S . DeepCoil-a fast and accurate prediction of coiled-coil domains in protein sequences. Bioinformatics. 2019; 35(16):2790-2795. DOI: 10.1093/bioinformatics/bty1062. View

5.
Manka S, Moores C . Microtubule structure by cryo-EM: snapshots of dynamic instability. Essays Biochem. 2018; 62(6):737-751. PMC: 6281474. DOI: 10.1042/EBC20180031. View