학술논문

Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12
Document Type
article
Source
Communications Biology. 4(1)
Subject
Biochemistry and Cell Biology
Biomedical and Clinical Sciences
Oncology and Carcinogenesis
Biological Sciences
Genetics
Cancer
Animals
Cell Cycle Proteins
Cell Line
Tumor
Centrosome
Gene Expression
Humans
Mice
Synaptonemal Complex
Biological sciences
Biomedical and clinical sciences
Language
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.