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Spatiotemporal regulations of Wee1 at the G2/M transition
Authors:Masuda Hirohisa  Fong Chii Shyang  Ohtsuki Chizuru  Haraguchi Tokuko  Hiraoka Yasushi
Institution:aLaboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln’s Inn Fields Laboratories, London WC2A 3LY, United Kingdom;bKobe Advanced ICT Research Center, National Institute of Information and Communications Technology, Kobe 651-2492, Japan;cGraduate School of Science, Osaka University, Toyonaka 560-0043, Japan;dGraduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan;Columbia University
Abstract:Wee1 is a protein kinase that negatively regulates mitotic entry in G2 phase by suppressing cyclin B-Cdc2 activity, but its spatiotemporal regulations remain to be elucidated. We observe the dynamic behavior of Wee1 in Schizosaccharomyces pombe cells and manipulate its localization and kinase activity to study its function. At late G2, nuclear Wee1 efficiently suppresses cyclin B-Cdc2 around the spindle pole body (SPB). During the G2/M transition when cyclin B-Cdc2 is highly enriched at the SPB, Wee1 temporally accumulates at the nuclear face of the SPB in a cyclin B-Cdc2-dependent manner and locally suppresses both cyclin B-Cdc2 activity and spindle assembly to counteract a Polo kinase-dependent positive feedback loop. Then Wee1 disappears from the SPB during spindle assembly. We propose that regulation of Wee1 localization around the SPB during the G2/M transition is important for proper mitotic entry and progression.
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