Ro Hyunju, Jang Youngjoo, Rhee Myungchull
School of Biosciences and Biotechnology, Chungnam National University, Daejeon 305-764, Korea.
Mol Cells. 2004 Feb 29;17(1):160-5.
Siah is a mammalian homologue of Drosophila seven in absentia (sina) that is required for R7 photoreceptor development. Both the SINA and Siah family interact with ubiquitin-conjugating enzymes via an N-terminal RING domain and the C-terminal domain of SINA/ Siahs interacts with proteins targeted for degradation. Siah induces cell growth arrest by promoting beta-catenin degradation in a phosphorylation-independent manner as a result of indirect binding to beta-catenin. We previously cloned a zebrafish homologue (Siaz) of Siah. Siaz shares high sequence homology with vertebrate Siah-2. We have now examined the role of Siaz in growth regulation using the trypan blue exclusion assay and flow cytometry and found that Siaz induces cellular growth arrest by inhibiting the G2/M transition. The C-terminal domain of Siaz that interacts with target proteins is not required for growth inhibition. We conclude that the N-terminal RING and central domain of Siaz are sufficient to block the G2/M phase transition.
Siah是果蝇无七(sina)的哺乳动物同源物,是R7光感受器发育所必需的。SINA和Siah家族都通过N端RING结构域与泛素结合酶相互作用,SINA/Siahs的C端结构域与靶向降解的蛋白质相互作用。Siah通过间接结合β-连环蛋白,以磷酸化非依赖的方式促进β-连环蛋白降解,从而诱导细胞生长停滞。我们之前克隆了Siah的斑马鱼同源物(Siaz)。Siaz与脊椎动物Siah-2具有高度的序列同源性。我们现在使用台盼蓝排斥试验和流式细胞术研究了Siaz在生长调节中的作用,发现Siaz通过抑制G2/M期转换诱导细胞生长停滞。与靶蛋白相互作用的Siaz的C端结构域对于生长抑制不是必需的。我们得出结论,Siaz的N端RING结构域和中央结构域足以阻断G2/M期转换。