Matsumoto Akinobu, Onoyama Ichiro, Nakayama Keiichi I
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
Biochem Biophys Res Commun. 2006 Nov 10;350(1):114-9. doi: 10.1016/j.bbrc.2006.09.003. Epub 2006 Sep 12.
Fbxw7 is the F-box protein component of an SCF-type ubiquitin ligase that contributes to the ubiquitin-dependent degradation of cell cycle activators and oncoproteins. Three isoforms (alpha, beta, and gamma) of Fbxw7 are produced from mRNAs with distinct 5' exons. We have now investigated regulation of Fbxw7 expression in mouse tissues. Fbxw7alpha mRNA was present in all tissues examined, whereas Fbxw7beta mRNA was detected only in brain and testis, and Fbxw7gamma mRNA in heart and skeletal muscle. The amount of Fbxw7alpha mRNA was high during quiescence (G0 phase) in mouse embryonic fibroblasts (MEFs) and T cells, but it decreased markedly as these cells entered the cell cycle. The abundance of Fbxw7alpha mRNA was unaffected by cell irradiation or p53 status. In contrast, X-irradiation increased the amount of Fbxw7beta mRNA in wild-type MEFs but not in those from p53-deficient mice, suggesting that radiation-induced up-regulation of p53 leads to production of Fbxw7beta mRNA. Our results thus indicate that expression of Fbxw7 isoforms is differentially regulated in a cell cycle- or p53-dependent manner.
Fbxw7是SCF型泛素连接酶的F-box蛋白成分，它参与细胞周期激活因子和癌蛋白的泛素依赖性降解。Fbxw7有三种异构体（α、β和γ），由具有不同5'外显子的mRNA产生。我们现在研究了小鼠组织中Fbxw7表达的调控。在所检测的所有组织中均存在Fbxw7α mRNA，而仅在脑和睾丸中检测到Fbxw7β mRNA，在心脏和骨骼肌中检测到Fbxw7γ mRNA。在小鼠胚胎成纤维细胞（MEF）和T细胞处于静止期（G0期）时，Fbxw7α mRNA的量很高，但随着这些细胞进入细胞周期，其明显减少。Fbxw7α mRNA的丰度不受细胞辐射或p53状态的影响。相反，X射线照射增加了野生型MEF中Fbxw7β mRNA的量，但在p53缺陷小鼠的MEF中则没有增加，这表明辐射诱导的p53上调导致Fbxw7β mRNA的产生。因此，我们的结果表明，Fbxw7异构体的表达以细胞周期或p53依赖性方式受到差异调节。
