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

Title: Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12
Authors: Sandhu S; Sou IF; Hunter JE; Salmon L; Wilson CL; Perkins ND; Hunter N; Davies OR; McClurg UL
Source: Communications Biology, December 2021
Publisher Information: Nature Research
Publication Year: 2021
Collection: Newcastle University Library ePrints Service
Description: © 2021, The Author(s).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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
Relation: https://eprints.ncl.ac.uk/279118; https://eprints.ncl.ac.uk/fulltext.aspx?url=279118/C303C26C-15D8-4633-9F32-3F8C6FF062F0.pdf&pub_id=279118
Availability: https://eprints.ncl.ac.uk/279118
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.8050AEBB
Database: BASE