Lo R S, Massagué J
Cell Biology Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nat Cell Biol. 1999 Dec;1(8):472-8. doi: 10.1038/70258.
SMAD proteins are phosphorylated by transforming growth factor-beta (TGF-beta) 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-beta ensures the irreversible termination of its own signalling function.
SMAD蛋白被转化生长因子-β（TGF-β）受体磷酸化后转移至细胞核，在细胞核中控制转录。在此，我们研究活化的Smad2的命运。我们发现受体介导的活化导致Smad2发生多聚泛素化，并随后被蛋白酶体降解。Smad2的泛素化是其在细胞核中积累的结果。如果避免降解，磷酸化的Smad2将以活性状态保留在细胞核中。通过将Smad2靶向降解，TGF-β确保其自身信号功能的不可逆终止。
