title: Potentiation of Smad-mediated transcriptional activation by the RNA-binding protein RBPMS.
abstract: Smad2, Smad3 and Smad4 proteins are considered to be key mediators of transforming growth factor-beta (TGF-beta) signaling. However, the identities of the Smad partners mediating TGF-beta signaling are not fully understood. Here, we show that RNA-binding protein with multiple splicing (RBPMS), a member of the RNA-binding protein family, physically interacts with Smad2, Smad3 and Smad4 both in vitro and in vivo. The presence of TGF-beta increases the binding of RBPMS with these Smad proteins. Consistent with the binding results, overexpression of RBPMS enhances Smad-dependent transcriptional activity in a TGF-beta-dependent manner, whereas knockdown of RBPMS decreases this activity. RBPMS interacts with TGF-beta receptor type I (TbetaR-I), increases phosphorylation of C-terminal SSXS regions in Smad2 and Smad3, and promotes the nuclear accumulation of the Smad proteins. Moreover, RBPMS fails to enhance the transcriptional activity of Smad2 and Smad3 that lack the C-terminal phosphorylation sites. Our data provide the first evidence for an RNA-binding protein playing a role in regulation of Smad-mediated transcriptional activity and suggest that RBPMS stimulates Smad-mediated transactivation possibly through enhanced phosphorylation of Smad2 and Smad3 at the C-terminus and promotion of the nuclear accumulation of the Smad proteins.
authors.affiliation: Beijing Institute of Biotechnology, Beijing, 100850 People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Lihua
authors.initials: L
authors.lastname: Ding
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Juqiang
authors.initials: J
authors.lastname: Han
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jiezhi
authors.initials: J
authors.lastname: Li
authors.forename: Haifeng
authors.initials: H
authors.lastname: Song
authors.forename: Qinong
authors.initials: Q
authors.lastname: Ye
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D051785:Smad Proteins / Q000378:metabolism*; D051899:Smad2 Protein / Q000737:chemistry / Q000378:metabolism; D051900:Smad3 Protein / Q000737:chemistry / Q000378:metabolism; D051901:Smad4 Protein / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
chemical_list: C101827:RBPMS protein, human; D016601:RNA-Binding Proteins; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1