@article {Wintere202201367, author = {Lilli Winter and Monika Kustermann and B{\"u}sra Ernhofer and Harald H{\"o}ger and Reginald E Bittner and Wolfgang M Schmidt}, title = {Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome}, volume = {5}, number = {11}, elocation-id = {e202201367}, year = {2022}, doi = {10.26508/lsa.202201367}, publisher = {Life Science Alliance}, abstract = {Aberrant expression of dystrophin, utrophin, dysferlin, or calpain-3 was originally identified in muscular dystrophies (MDs). Increasing evidence now indicates that these proteins might act as tumor suppressors in myogenic and non-myogenic cancers. As DNA damage and somatic aneuploidy, hallmarks of cancer, are early pathological signs in MDs, we hypothesized that a common pathway might involve the centrosome. Here, we show that dystrophin, utrophin, dysferlin, and calpain-3 are functional constituents of the centrosome. In myoblasts, lack of any of these proteins caused excess centrosomes, centrosome misorientation, nuclear abnormalities, and impaired microtubule nucleation. In dystrophin double-mutants, these defects were significantly aggravated. Moreover, we demonstrate that also in non-myogenic cells, all four MD-related proteins localize to the centrosome, including the muscle-specific full-length dystrophin isoform. Therefore, MD-related proteins might share a convergent function at the centrosome in addition to their diverse, well-established muscle-specific functions. Thus, our findings support the notion that cancer-like centrosome-related defects underlie MDs and establish a novel concept linking MDs to cancer.}, URL = {https://www.life-science-alliance.org/content/5/11/e202201367}, eprint = {https://www.life-science-alliance.org/content/5/11/e202201367.full.pdf}, journal = {Life Science Alliance} }