The Ski oncoprotein interacts with the Smad proteins to repress TGFβ signaling

K Luo, SL Stroschein, W Wang, D Chen… - Genes & …, 1999 - genesdev.cshlp.org
K Luo, SL Stroschein, W Wang, D Chen, E Martens, S Zhou, Q Zhou
Genes & development, 1999genesdev.cshlp.org
Smad proteins are critical signal transducers downstream of the receptors of the
transforming growth factor-β (TGFβ) superfamily. On phosphorylation and activation by the
active TGFβ receptor complex, Smad2 and Smad3 form hetero-oligomers with Smad4 and
translocate into the nucleus, where they interact with different cellular partners, bind to DNA,
regulate transcription of various downstream response genes, and cross-talk with other
signaling pathways. Here we show that a nuclear oncoprotein, Ski, can interact directly with …
Smad proteins are critical signal transducers downstream of the receptors of the transforming growth factor-β (TGFβ) superfamily. On phosphorylation and activation by the active TGFβ receptor complex, Smad2 and Smad3 form hetero-oligomers with Smad4 and translocate into the nucleus, where they interact with different cellular partners, bind to DNA, regulate transcription of various downstream response genes, and cross-talk with other signaling pathways. Here we show that a nuclear oncoprotein, Ski, can interact directly with Smad2, Smad3, and Smad4 on a TGFβ-responsive promoter element and repress their abilities to activate transcription through recruitment of the nuclear transcriptional corepressor N-CoR and possibly its associated histone deacetylase complex. Overexpression of Ski in a TGFβ-responsive cell line renders it resistant to TGFβ-induced growth inhibition and defective in activation of JunB expression. This ability to overcome TGFβ-induced growth arrest may be responsible for the transforming activity of Ski in human and avian cancer cells. Our studies suggest a new paradigm for inactivation of the Smad proteins by an oncoprotein through transcriptional repression.
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