Progression through mitosis, the cell cycle phase deputed to segregate replicated chromosomes, is granted by a protein phosphorylation wave that follows an activation-inactivation cycle of cyclin B-dependent kinase (Cdk) 1, the major mitosis-promoting enzyme. To ensure correct chromosome segregation, the safeguard mechanism spindle assembly checkpoint (SAC) delays Cdk1 inactivation by preventing cyclin B degradation until mitotic spindle assembly. At the end of mitosis, reversal of bulk mitotic protein phosphorylation, downstream Cdk1 inactivation, is required to complete mitosis and crucially relies on the activity of major protein phosphatases like PP2A. A role for PP2A, however, has also been suggested in spindle assembly and SAC-dependent control of Cdk1. Indeed, PP2A was found in complex with SAC proteins while small interfering RNAs (siRNAs)-mediated downregulation of PP2A holoenzyme components affected mitosis completion in mammalian cells. However, whether the SAC-dependent control of Cdk1 required the catalytic activity of PP2A has never been directly assessed. Here, using two PP2A inhibitors, okadaic acid and LB-100, we provide evidence that PP2A activity is dispensable for SAC control of Cdk1 in human cells.

Evidence that PP2A activity is dispensable for spindle assembly checkpoint-dependent control of Cdk1 / Cervone, N; Monica, R. D.; Serpico, A. F.; Vetrei, C; Scaraglio, M; Visconti, R; Grieco, Domenico. - In: ONCOTARGET. - ISSN 1949-2553. - 9:7(2018), pp. 7312-7321. [10.18632/oncotarget.23329]

Evidence that PP2A activity is dispensable for spindle assembly checkpoint-dependent control of Cdk1

Cervone N;Vetrei C;Grieco Domenico
Ultimo
Conceptualization
2018

Abstract

Progression through mitosis, the cell cycle phase deputed to segregate replicated chromosomes, is granted by a protein phosphorylation wave that follows an activation-inactivation cycle of cyclin B-dependent kinase (Cdk) 1, the major mitosis-promoting enzyme. To ensure correct chromosome segregation, the safeguard mechanism spindle assembly checkpoint (SAC) delays Cdk1 inactivation by preventing cyclin B degradation until mitotic spindle assembly. At the end of mitosis, reversal of bulk mitotic protein phosphorylation, downstream Cdk1 inactivation, is required to complete mitosis and crucially relies on the activity of major protein phosphatases like PP2A. A role for PP2A, however, has also been suggested in spindle assembly and SAC-dependent control of Cdk1. Indeed, PP2A was found in complex with SAC proteins while small interfering RNAs (siRNAs)-mediated downregulation of PP2A holoenzyme components affected mitosis completion in mammalian cells. However, whether the SAC-dependent control of Cdk1 required the catalytic activity of PP2A has never been directly assessed. Here, using two PP2A inhibitors, okadaic acid and LB-100, we provide evidence that PP2A activity is dispensable for SAC control of Cdk1 in human cells.
2018
Evidence that PP2A activity is dispensable for spindle assembly checkpoint-dependent control of Cdk1 / Cervone, N; Monica, R. D.; Serpico, A. F.; Vetrei, C; Scaraglio, M; Visconti, R; Grieco, Domenico. - In: ONCOTARGET. - ISSN 1949-2553. - 9:7(2018), pp. 7312-7321. [10.18632/oncotarget.23329]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/772106
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