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
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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Auteurs

Lilli Winter (L)

Neuromuscular Research Department, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.

Monika Kustermann (M)

Neuromuscular Research Department, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.

Büsra Ernhofer (B)

Neuromuscular Research Department, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.

Harald Höger (H)

Division for Laboratory Animal Science and Genetics, Medical University of Vienna, Himberg, Austria.

Reginald E Bittner (RE)

Neuromuscular Research Department, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria wolfgang.schmidt@meduniwien.ac.at reginald.bittner@meduniwien.ac.at.

Wolfgang M Schmidt (WM)

Neuromuscular Research Department, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria wolfgang.schmidt@meduniwien.ac.at reginald.bittner@meduniwien.ac.at.

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Classifications MeSH