Regulation of mitotic events by the nucleolar phosphatase Cdc14B

Research group leader: PD Dr. Renate Voit

A model depicting the role of Cdc14B during mitosis. Cdc14B promotes progression through mitosis by dephosphorylating Cdc25 and TAFI110, the largest subunit of the TBP-TAF complex SL1

Entry into mitosis is triggered by activation of the cyclin-dependent kinase Cdk1/cyclin B, which phosphorylates a variety of substrates to drive progression through mitosis. On search for phosphatases that reverse Cdk1/cyclin B phosphorylations and restrain Cdk1 activity to mitosis, we found that Cdc14B, the mammalian homologue of yeast Cdc14, is a key regulator of mitosis. RNAi-mediated depletion of hCdc14B causes numerous mitotic defects, including hyperphosphorylation of Cdc25 and prolongation of Cdk1/cyclin B activity, leading to mitotic arrest and cell death. Cdc14B disrupts the positive feedback loop between Cdk1 and Cdc25, which ensures high Cdk1/cyclin B activity in early mitosis. Moreover, Cdc14B relieves mitotic repression of Pol I transcription by specific dephosphorylation of TAFI110, a subunit of the basal transcription factor SL1. Thus, Cdc14B plays a pivotal role in M/G1 progression by inactivating Cdk1/cyclin B and removing inhibitory phosphate groups from target proteins (Voit et al 2015).

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