Abstract
The transcription factor Smad2 is released from cytoplasmic retention by TGFβ receptor-mediated phosphorylation, accumulating in the nucleus where it associates with cofactors to regulate transcription. We uncovered direct interactions of Smad2 with the nucleoporins CAN/Nup214 and Nup153. These interactions mediate constitutive nucleocytoplasmic shuttling of Smad2. CAN/Nup214 and Nup153 compete with the cytoplasmic retention factor SARA and the nuclear Smad2 partner FAST-1 for binding to a hydrophobic corridor on the MH2 surface of Smad2. TGFβ receptor-mediated phosphorylation stimulates nuclear accumulation of Smad2 by modifying its affinity for SARA and Smad4 but not for CAN/Nup214 or Nup153. Thus, by directly contacting the nuclear pore complex, Smad2 undergoes constant shuttling, providing a dynamic pool that is competitively drawn by cytoplasmic and nuclear signal transduction partners.
Original language | English (US) |
---|---|
Pages (from-to) | 271-282 |
Number of pages | 12 |
Journal | Molecular Cell |
Volume | 10 |
Issue number | 2 |
DOIs | |
State | Published - Aug 2002 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology