Shi Jianli, Zhao Ying, Vonderfecht Tyson, Winey Mark, Klymkowsky Michael W
Molecular, Cellular &Developmental Biology University of Colorado Boulder, Boulder, Colorado 80309.
Sci Rep. 2015 May 27;5:10283. doi: 10.1038/srep10283.
Centrins (Cetns) are highly conserved, widely expressed, and multifunctional Ca(2+)-binding eukaryotic signature proteins best known for their roles in ciliogenesis and as critical components of the global genome nucleotide excision repair system. Two distinct Cetn subtypes, Cetn2-like and Cetn3-like, have been recognized and implicated in a range of cellular processes. In the course of morpholino-based loss of function studies in Xenopus laevis, we have identified a previously unreported Cetn2-specific function, namely in fibroblast growth factor (FGF) mediated signaling, specifically through the regulation of FGF and FGF receptor RNA levels. Cetn2 was found associated with the RNA polymerase II binding sites of the Cetn2-regulated FGF8 and FGFR1a genes, but not at the promoter of a gene (BMP4) whose expression was altered indirectly in Cent2 morphant embryos. These observations point to a previously unexpected role of Cetn2 in the regulation of gene expression and embryonic development.
中心蛋白(Centrins,Cetns)是高度保守、广泛表达且多功能的Ca(2+)结合真核生物标志性蛋白,因其在纤毛发生中的作用以及作为全球基因组核苷酸切除修复系统的关键组分而最为人所知。已识别出两种不同的Cetn亚型,即Cetn2样和Cetn3样,并发现它们参与一系列细胞过程。在基于吗啉代的非洲爪蟾功能丧失研究过程中,我们鉴定出一种以前未报道的Cetn2特异性功能,即在成纤维细胞生长因子(FGF)介导的信号传导中,特别是通过调节FGF和FGF受体RNA水平发挥作用。发现Cetn2与Cetn2调节的FGF8和FGFR1a基因的RNA聚合酶II结合位点相关,但与基因(BMP4)的启动子无关,该基因在Cent2 morphant胚胎中的表达间接改变。这些观察结果表明Cetn2在基因表达调控和胚胎发育中具有以前未预料到的作用。