Collart Clara, Remacle Jacques E, Barabino Silvia, van Grunsven Leo A, Nelles Luc, Schellens Ann, Van de Putte Tom, Pype Stefan, Huylebroeck Danny, Verschueren Kristin
Department of Developmental Biology, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, B-3000 Leuven, Belgium.
Genes Cells. 2005 Sep;10(9):897-906. doi: 10.1111/j.1365-2443.2005.00887.x.
Ligand-bound receptors of the Transforming Growth Factor-beta (TGF-beta) family promote the formation of complexes between Smad proteins that subsequently accumulate in the nucleus and interact there with other transcriptional regulators, leading to modulation of target gene expression. We identified a novel nuclear protein, Smicl, which binds to Smad proteins. Smicl and Smads cooperate and enhance TGF-beta mediated activation of a Smad-responsive reporter gene. A domain with five CCCH-type zinc fingers in Smicl is structurally and functionally, at least in vitro, similar to a domain in CPSF-30, the 30 kDa subunit of Cleavage and Polyadenylation Specificity Factor (CPSF). Like CPSF-30, Smicl can associate with some other CPSF subunits characterized previously. Its effect on the induction of a reporter gene for TGF-beta requires the cleavage/polyadenylation signal downstream of the coding sequence of that gene. Thus, Smicl is a novel protein that displays CPSF-30-like activities, interacts in the nucleus with activated Smads, and potentiates in TGF-beta stimulated cells Smad-dependent transcriptional responses, possibly in conjunction with the activity of CPSF complexes.
转化生长因子-β（TGF-β）家族的配体结合受体促进Smad蛋白之间形成复合物，这些复合物随后在细胞核中积累并在那里与其他转录调节因子相互作用，从而导致靶基因表达的调节。我们鉴定出一种新型核蛋白Smicl，它能与Smad蛋白结合。Smicl与Smad蛋白协同作用，增强TGF-β介导的Smad反应性报告基因的激活。Smicl中具有五个CCCH型锌指的结构域在结构和功能上，至少在体外，类似于切割和聚腺苷酸化特异性因子（CPSF）的30 kDa亚基CPSF-30中的一个结构域。与CPSF-30一样，Smicl可以与先前鉴定的一些其他CPSF亚基结合。它对TGF-β报告基因诱导的作用需要该基因编码序列下游的切割/聚腺苷酸化信号。因此，Smicl是一种新型蛋白质，具有类似CPSF-30的活性，在细胞核中与活化的Smad蛋白相互作用，并在TGF-β刺激的细胞中增强Smad依赖性转录反应，可能与CPSF复合物的活性协同作用。
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