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Media type:
E-Article
Title:
Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome
Contributor:
Winter, Lilli;
Kustermann, Monika;
Ernhofer, Büsra;
Höger, Harald;
Bittner, Reginald E;
Schmidt, Wolfgang M
Published:
Life Science Alliance, LLC, 2022
Published in:
Life Science Alliance, 5 (2022) 11, Seite e202201367
Language:
English
DOI:
10.26508/lsa.202201367
ISSN:
2575-1077
Origination:
Footnote:
Description:
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.