The ubiquitin–proteasome system is an essential regulator of Acf7, which serves as a key effector for themaintenance of the EMT program and migration. However, the precise mechanism for the deubiquitination ofAcf7 is still not fully understood. Using a proteomic approach, we identified ubiquitin-specific peptidase 14(USP14) as an Acf7-associated deubiquitinase. Our findings show that there was an interaction between USP14and Acf7. The expression of USP14 and Acf7 were elevated in lung cancer tissues compared to adjacentnormal cells. Employing the overexpression of USP14 and the USP14 knockdown assay indicated that USP14can greatly increase the steady-state levels of Acf7 by inhibiting the degradation of Acf7 through the ubiquitin–proteasome pathway. Here we identified USP14 as a deubiquitinating enzyme that regulated Acf7 ubiquitinationand protein levels. Moreover, knockdown of USP14 inhibited cell migration, however, overexpressionof wild-type USP14 but not USP14 mutants promoted cell migration. Together, these results suggest thatUSP14 plays an important role in the NSCLC migration through modulating Acf7 stability.
Volume 46, 2021
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