Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12

Sandhu, Sumit, Sou, Ieng F, Hunter, Jill E, Salmon, Lucy, Wilson, Caroline L, Perkins, Neil D, Hunter, Neil, Davies, Owen R and McClurg, Urszula L ORCID: 0000-0003-2631-4174 (2021) Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12. COMMUNICATIONS BIOLOGY, 4 (1). 1371-.

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Official URL: http://dx.doi.org/10.1038/s42003-021-02887-4

Abstract

The synaptonemal complex (SC) is a supramolecular protein scaffold that mediates chromosome synapsis and facilitates crossing over during meiosis. In mammals, SC proteins are generally assumed to have no other function. Here, we show that SC protein TEX12 also localises to centrosomes during meiosis independently of chromosome synapsis. In somatic cells, ectopically expressed TEX12 similarly localises to centrosomes, where it is associated with centrosome amplification, a pathology correlated with cancer development. Indeed, TEX12 is identified as a cancer-testis antigen and proliferation of some cancer cells is TEX12-dependent. Moreover, somatic expression of TEX12 is aberrantly activated via retinoic acid signalling, which is commonly disregulated in cancer. Structure-function analysis reveals that phosphorylation of TEX12 on tyrosine 48 is important for centrosome amplification but not for recruitment of TEX12 to centrosomes. We conclude that TEX12 normally localises to meiotic centrosomes, but its misexpression in somatic cells can contribute to pathological amplification and dysfunction of centrosomes in cancers.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Tumor, Synaptonemal Complex, Centrosome, Animals, Humans, Mice, Cell Cycle Proteins, Gene Expression
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	08 Dec 2021 11:29
Last Modified:	18 Jan 2023 21:23
DOI:	10.1038/s42003-021-02887-4
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3144951