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Specificity Through Degradation

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Science  14 Jan 2005:
Vol. 307, Issue 5707, pp. 183
DOI: 10.1126/science.307.5707.183c

Yeast use partially overlapping kinase modules to specify discrete cellular responses. For example, the upstream kinases in the mitogen-activated protein kinase (MAPK) cascade, Ste11 and Ste7, are both activated during mating response signaling and during filamentous growth signaling. The MAPK Kss1 then triggers the filamentous growth transcriptional cascade and the MAPK Fus3 triggers the mating response genes. In the absence of Fus3, pheromone signaling stimulates Kss1 and filamentous growth gene expression, suggesting that Fus3 has a role in suppressing filamentous growth responses during pheromone signaling. Chou et al. and Bao et al. now report that Fus3 triggers the degradation of a transcription factor required for filamentous growth, Tec1, to maintain signaling specificity through the shared MAPK pathways. The abundance of Tec1 decreased after mating stimulated by pheromone and this destabilization required Fus3 but not Kss1. Tec1 Thr273 was phosphorylated by Fus3. Degradation was mediated by a SCF ubiquitin ligase complex. Thus, selective degradation of a transcriptional regulator represents a mechanism for generating specificity during intracellular signaling. — NG

Cell 119, 981 (2004).

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