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LUBRICHET CROZIER · ID: 12897-06. SOMAGNE MIGUIN · ID: 12897-05. MTV ILLUSTRATED The Tipsy Writer · ID: 12897-07.Pif and Cdc48-dependent degradation of dishevelled regulates wing growth in Drosophila.
The effector of the Wnt/Wingless pathway, dishevelled, is a scaffolding protein that can affect its own trafficking and stability. A truncated form of the ligand is sufficient to trigger the protein-trafficking-dependent degradation of dishevelled protein. The apical accumulation of the dishevelled protein depends on the activity of Wingless (Wg), and, in an adjacent cell, on the activity of a repressor that binds to the effector. Consequently, absence of dishevelled proteins in the adjacent cells triggers the up-regulation of Wg, and the signal is amplified up the gradient. Here, we show that this mechanism is similar for vertebrate dishevelled proteins, in Xenopus and Drosophila. The vertebrate and Drosophila homologues of the molecular chaperone Cdc48 (p97 in human, Ddf2 in Drosophila), which binds and segregates nascent polypeptides, are required for the activation of Wg and the associated degradation of dishevelled. The dishevelled protein accumulates in vesicles that associate with the centrosome, the site of the Wg transduction pathway in Drosophila. Therefore, the degradation machinery function is not restricted to the cytoplasm but includes the centrosome
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