Ubiquitin-dependent degradation of TGF-β-activated Smad2

SMAD proteins are phosphorylated by transforming growth factor-β (TGF-β) receptors and translocate to the nucleus, where they control transcription. Here we investigate the fate of activated Smad2. We show that receptor-mediated activation leads to multi-ubiquitination and subsequent degradation of Smad2 by the proteasome. Ubiquitination of Smad2 is a consequence of its accumulation in the nucleus. If degradation is averted, the phosphorylated Smad2 remains in the nucleus in an active state. By targeting Smad2 for destruction, TGF-β ensures the irreversible termination of its own signalling function.

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