Mol. Genet. Genom., in press

Rck2 degradation in high zinc is dependent on Pep4.

Swaminathan S, Sunnerhagen P


Department of Cell and Molecular Biology, Lundberg Laboratory, Göteborg University,  P.O. Box 462, SE-405 30 Göteborg, Sweden.

We find that the MAPK-activated protein kinase Rck2 of Saccharomyces cerevisiae is subject to intracellular degradation after exposure of cells to Zn2+ concentrations exceeding 5 mM. In undisturbed cells, Rck2 is a stable protein with a turnover time exceeding 60 min. In high zinc, most of the protein pool is degraded within 5 min. This degradation is blocked by inhibiting the vacuolar proteolytic pathway, as seen by adding the protease inhibitor phenyl methyl sulfonyl fluoride, and in pep4 mutants. By contrast, blocking the proteasomal pathway with the inhibitor MG132 does not stop Rck2 degradation upon addition of Zn2+, nor is degradation inhibited in the proteasomal mutants pre1 pre2, cim3, or cim5. The stability of Rck2 is not affected by other stress conditions examined, or by growth rate. Possible mechanisms and physiological significance of the degradation of Rck2 under high zinc conditions are discussed.