Mitogen-activated Protein Kinase Kinase 1-dependent Golgi Unlinking Occurs in G2 Phase and Promotes the G2/M Cell Cycle Transition

TN Feinstein, AD Linstedt - Molecular biology of the cell, 2007 - Am Soc Cell Biol
TN Feinstein, AD Linstedt
Molecular biology of the cell, 2007Am Soc Cell Biol
Two controversies have emerged regarding the signaling pathways that regulate Golgi
disassembly at the G2/M cell cycle transition. The first controversy concerns the role of
mitogen-activated protein kinase activator mitogen-activated protein kinase kinase (MEK) 1,
and the second controversy concerns the participation of Golgi structure in a novel cell cycle
“checkpoint.” A potential simultaneous resolution is suggested by the hypothesis that MEK1
triggers Golgi unlinking in late G2 to control G2/M kinetics. Here, we show that inhibition of …
Two controversies have emerged regarding the signaling pathways that regulate Golgi disassembly at the G2/M cell cycle transition. The first controversy concerns the role of mitogen-activated protein kinase activator mitogen-activated protein kinase kinase (MEK)1, and the second controversy concerns the participation of Golgi structure in a novel cell cycle “checkpoint.” A potential simultaneous resolution is suggested by the hypothesis that MEK1 triggers Golgi unlinking in late G2 to control G2/M kinetics. Here, we show that inhibition of MEK1 by RNA interference or by using the MEK1/2-specific inhibitor U0126 delayed the passage of synchronized HeLa cells into M phase. The MEK1 requirement for normal mitotic entry was abrogated if Golgi proteins were dispersed before M phase by treatment of cells with brefeldin A or if GRASP65, which links Golgi stacks into a ribbon network, was depleted. Imaging revealed that unlinking of the Golgi apparatus begins before M phase, is independent of cyclin-dependent kinase 1 activation, and requires MEK signaling. Furthermore, expression of the GRASP family member GRASP55 after alanine substitution of its MEK1-dependent mitotic phosphorylation sites inhibited both late G2 Golgi unlinking and the G2/M transition. Thus, MEK1 plays an in vivo role in Golgi reorganization, which regulates cell cycle progression.
Am Soc Cell Biol