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PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and Smad3
Author(s) -
Dai Fangyan,
Shen Tao,
Li Zhaoyong,
Lin Xia,
Feng XinHua
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.174
Subject(s) - dephosphorylation , nuclear export signal , phosphorylation , microbiology and biotechnology , smad2 protein , biology , phosphatase , transcription factor , signal transduction , nuclear localization sequence , signalling , nucleus , cell nucleus , biochemistry , gene , smad
Smad2 and Smad3 (Smad2/3) are essential signal transducers and transcription factors in the canonical transforming growth factor‐β (TGF‐β) signalling pathway. Active Smad2/3 signalling in the nucleus is terminated by dephosphorylation and subsequent nuclear export of Smad2/3. Here we report that protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through targeting nuclear exporter RanBP3. PPM1A directly interacted with and dephosphorylated RanBP3 at Ser 58 in vitro and in vivo . Consistently, RanBP3 phosphorylation was elevated in PPM1A‐null mouse embryonic fibroblasts. Dephosphorylation of RanBP3 at Ser 58 promoted its ability to export Smad2/3 and terminate TGF‐β responses. Our findings indicate the critical role of PPM1A in maximizing exporter activity of RanBP3 for efficient termination of canonical TGF‐β signalling.