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

时间:2011年10月28日 访问次数:1544

EMBO Rep. 2011 Oct 28;12(11):1175-81.

Fangyan Dai, Tao Shen, Zhaoyong Li, Xia Lin, Xin-Hua Feng*


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.