Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
10
01
2022
revised:
21
06
2022
accepted:
22
06
2022
entrez:
5
7
2022
pubmed:
6
7
2022
medline:
7
7
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35790299
pii: 5/11/e202201367
doi: 10.26508/lsa.202201367
pmc: PMC9259872
pii:
doi:
Substances chimiques
Dysferlin
0
Dystrophin
0
Membrane Proteins
0
Utrophin
0
Calpain
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022 Winter et al.
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