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Author:
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Clotet Bellmunt, Josep; Escoté, Xavier; Àngel Adrover, Miquel; Yaakov, Gilad; Garí Marsol, Eloi; Aldea, Martí; de Nadal, Eulàlia; Posas, Francesc
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Notes:
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Control of cell cycle progression by stress-activated protein
kinases (SAPKs) is essential for cell adaptation to extracellular
stimuli. Exposure of yeast to osmostress leads
to activation of the Hog1 SAPK, which controls cell cycle
at G1 by the targeting of Sic1. Here, we show that survival
to osmostress also requires regulation of G2 progression.
Activated Hog1 interacts and directly phosphorylates a
residue within the Hsl7-docking site of the Hsl1 checkpoint
kinase, which results in delocalization of Hsl7 from
the septin ring and leads to Swe1 accumulation. Upon
Hog1 activation, cells containing a nonphosphorylatable
Hsl1 by Hog1 are unable to promote Hsl7 delocalization,
fail to arrest at G2 and become sensitive to osmostress.
Together, we present a novel mechanism that regulates the
Hsl1–Hsl7 complex to integrate stress signals to mediate
cell cycle arrest and, demonstrate that a single MAPK
coordinately modulates different cell cycle checkpoints to
improve cell survival upon stress.
We thank Y Barral, J Ayté, E Herrero, S Moreno, M Winey, A Casamayor, G Gil and G Ammerer for valuable advice, plasmids and strains; O` scar Fornas, Laia Subirana and Marisa Rodriguez for their excellent technical assistance. XE was recipient of an FPI fellowship (MEC, Spanish Government) and MA Adrover is recipient of an FPU fellowship (MEC). We declare that we have no financial conflict of interest. This work was supported by grants from Ministerio de Ciencia y Tecnologı´a (BMC2003-00321), ‘Distincio´ de la Generalitat de Catalunya per a la Promocio´ de la Recerca Universitaria, Joves Investigadors’ DURSI (Generalitat de Catalunya) and the EURYI program (ESF) to FP. |
