| First Author | Winter L | Year | 2022 |
| Journal | Life Sci Alliance | Volume | 5 |
| Issue | 11 | PubMed ID | 35790299 |
| Mgi Jnum | J:328223 | Mgi Id | MGI:7326564 |
| Doi | 10.26508/lsa.202201367 | Citation | Winter L, et al. (2022) Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome. Life Sci Alliance 5(11):e202201367 |
| abstractText | 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. |
