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PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and Smad3.

ABSTRACT: Smad2 and Smad3 (Smad2/3) are essential signal transducers and transcription factors in the canonical transforming growth factor-? (TGF-?) 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-? responses. Our findings indicate the critical role of PPM1A in maximizing exporter activity of RanBP3 for efficient termination of canonical TGF-? signalling.

SUBMITTER: Dai F

PROVIDER: S-EPMC3207100 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and Smad3.

Dai Fangyan F Shen Tao T Li Zhaoyong Z Lin Xia X Feng Xin-Hua XH

EMBO reports 20111028 11

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. Con ...[more]

PMID: 21960005

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