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Dev Cell. 2009 Mar;16(3):345-57. doi: 10.1016/j.devcel.2009.01.022.

Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling.

Author information

1
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

Smad2 and Smad3 (Smad2/3) are key intracellular signal transducers for TGF-beta signaling, and their transcriptional activities are controlled through reversible phosphorylation and nucleocytoplasmic shuttling. However, the precise mechanism underlying nuclear export of Smad2/3 remains elusive. Here we report the essential function of RanBP3 in selective nuclear export of Smad2/3 in the TGF-beta pathway. RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner. As a result, increased expression of RanBP3 inhibits TGF-beta signaling in mammalian cells and Xenopus embryos. Conversely, depletion of RanBP3 expression or dominant-negative inhibition of RanBP3 enhances TGFbeta-induced antiproliferative and transcriptional responses. In conclusion, our study supports a definitive role for RanBP3 in mediating Smad2/3 nuclear export and terminating TGF-beta signaling.

PMID:
19289081
PMCID:
PMC2676691
DOI:
10.1016/j.devcel.2009.01.022
[Indexed for MEDLINE]
Free PMC Article

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