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Impaired reorganization of centrosome structure underlies human congenital dilated cardiomyopathy

ABSTRACT: During cardiomyocyte (CM) maturation, the centrosome undergoes a dramatic structural reorganization whereby certain components, previously localized at the centrioles, become localized to the nuclear envelope. Here, we generated a scRNA-seq data set of iPSC-CMs and identified impaired CM maturation as a key dysregulated process underlying a case of congenital dilated cardiomyopathy

ORGANISM(S): Homo sapiens

PROVIDER: GSE184899 | GEO | 2022/03/05

REPOSITORIES: GEO

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Impaired reorganization of centrosome structure underlies human congenital dilated cardiomyopathy

Project description:Impaired reorganization of centrosome structure underlies human congenital dilated cardiomyopathy

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Project description:Centrosomal protein 120 (CEP120) is a 120kD centrosome protein that plays an important role in centrosome replication. Overexpression of CEP120 can lead to centrosome amplification, which is closely associated with tumorigenesis and development. However, there are no reports on the relationship between CEP120 and tumors. In our study, overexpression of CEP120 promoted centrosome amplification in gastric cancer (GC), and the role of CEP120 in promoting GC progression was demonstrated in vitro and in vivo. We demonstrated that CEP120 promotes centrosome amplification and GC progression by promoting the expression and centrosome aggregation of the deubiquitinating enzyme USP54, maintaining the stability of PLK4 and reducing its ubiquitination degradation. In conclusion, the CEP120-USP54-PLK4 axis may play an important role in promoting centrosome amplification and GC progression, thus providing a potential therapeutic target for GC.

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CEP44 ensures the formation of bona fide centriole wall, a requirement for the centriole-to-centrosome conversion

Project description:The centriole-to-centrosome conversion is a mechanism of the centrosome maturation process that depends on the formation of a proper centriole wall structure. Beside the centriole wall biogenesis factors TUBD1 and TUBE1, CEP44 is involved in this process. Lack of CEP44 generates defects in the centriole wall structure and thus, it interferes with the centrosome maturation. POC1B was found to be an interactor of CEP44 in the immunoprecipitation and LC-MS experiment. The interaction and the function of this hit was validated with further independent biological experiments.

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