Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFβ signaling complexes in the cytoplasm and nucleus Journal Article

  

Authors:	Xu, L.; Kang, Y.; Col, S.; Massagué, J.
Article Title:	Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFβ signaling complexes in the cytoplasm and nucleus
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.
Keywords:	signal transduction; controlled study; protein phosphorylation; unclassified drug; human cell; dna-binding proteins; nonhuman; binding affinity; protein domain; animal cell; mouse; animals; mice; smad protein; smad2 protein; transforming growth factor beta; protein protein interaction; molecular dynamics; cell line; protein binding; hela cell; hela cells; cos cells; animalia; nucleocytoplasmic transport; peptide fragments; protein transport; cell strain cos1; transforming growth factor beta receptor; cytoplasm; active transport, cell nucleus; trans-activators; cell nucleus; cell strain 3t3; protein derivative; 3t3 cells; receptors, cytoplasmic and nuclear; nuclear pore complex proteins; karyopherins; hydrophobicity; nuclear pore; nucleoporin; nuclear pore complex; smad anchor for receptor activation; cytoplasm protein; protein nup214; nuclear import; humans; human; article; protein can; protein fast 1; protein nup153
Journal Title:	Molecular Cell
Volume:	10
Issue:	2
ISSN:	1097-2765
Publisher:	Cell Press
Date Published:	2002-08-01
Start Page:	271
End Page:	282
Language:	English
DOI:	10.1016/s1097-2765(02)00586-5
PUBMED:	12191473
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0036670359&partnerID=40&md5=11402a0787e33daccbfe00d618450a84
Notes:	Export Date: 14 November 2014 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/67078