Abstract
The key kinase Cdk1 (Cdc2) promotes irreversible mitotic entry mainly by activating the phosphatase Cdc25 while suppressing the tyrosine kinase Wee1. Wee1 needs to be down-regulated at the onset of mitosis to ensure rapid activation of Cdk1. In human somatic cells, one mechanism of suppressing Wee1 activity is mediated by ubiquitylation-dependent proteolysis through the Skp1/Cul1/F-box protein (SCF) ubiquitin E3 ligase complex. This mechanism is believed to be conserved from yeasts to humans. So far, the best characterized human F-box proteins involved in recognition of Wee1 are β-TrCP and Tome-1. Although fission yeast Wee1 is the first identified member of its conserved kinase family, the F-box proteins involved in recognition and ubiquitylation of Wee1 have not been identified in this organism. In this study, our screen using Wee1-Renilla luciferase as the reporter revealed that two F-box proteins Pof1 and Pof3 are required for downregulating Wee1 and are possibly responsible for recruiting Wee1 to SCF. Our genetic analyses supported a functional relevance between Pof1 and Pof3 and the rate of mitotic entry, and Pof3 might play a major role in this process.
- Received February 20, 2017.
- Accepted December 12, 2017.
- © 2017. Published by The Company of Biologists Ltd
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