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USP49 deubiquitinase regulates the mitotic spindle checkpoint and prevents aneuploidy.

ABSTRACT: The spindle assembly checkpoint (SAC) is an essential mechanism that ensures the accurate chromosome segregation during mitosis, thus preventing genomic instability. Deubiquitinases have emerged as key regulators of the SAC, mainly by determining the fate of proteins during cell cycle progression. Here, we identify USP49 deubiquitinase as a novel regulator of the spindle checkpoint. We show that loss of USP49 in different cancer cell lines impairs proliferation and increases aneuploidy. In addition, USP49-depleted cells overcome the arrest induced by the SAC in the presence of nocodazole. Finally, we report new binding partners of USP49, including ribophorin 1, USP44, and different centrins.

SUBMITTER: Campos-Iglesias D

PROVIDER: S-EPMC9879932 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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USP49 deubiquitinase regulates the mitotic spindle checkpoint and prevents aneuploidy.

Campos-Iglesias Diana D Fraile Julia M JM Bretones Gabriel G Montero Alejandro A AA Bonzon-Kulichenko Elena E Vázquez Jesús J López-Otín Carlos C Freije José M P JMP

Cell death & disease 20230126 1

The spindle assembly checkpoint (SAC) is an essential mechanism that ensures the accurate chromosome segregation during mitosis, thus preventing genomic instability. Deubiquitinases have emerged as key regulators of the SAC, mainly by determining the fate of proteins during cell cycle progression. Here, we identify USP49 deubiquitinase as a novel regulator of the spindle checkpoint. We show that loss of USP49 in different cancer cell lines impairs proliferation and increases aneuploidy. In addit ...[more]

PMID: 36702832

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