Orphan nuclear receptor Nur77 accelerates the initial phase of adipocyte differentiation in 3T3-L1 cells by promoting mitotic clonal expansion
Orphan nuclear receptor Nur77 accelerates the initial phase of adipocyte differentiation in 3T3-L1 cells by promoting mitotic clonal expansion
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DOI：
10.1093/jb/mvm018
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发表时间：
2007-02-01
影响因子：
2.7
通讯作者：
Osumi, Takashi
中科院分区：
文献类型：
--
作者：
Fumoto, Toshio;Yamaguchi, Tomohiro;Osumi, Takashi
Nur77是核受体超家族中的孤儿成员，表达于多种类型的细胞中，并参与多种生物学过程。虽然Nur77mRNA在3T3-L1细胞成脂的早期就被诱导，但其作用尚不清楚。为了解决这个问题，我们密切观察了Nur77mRNA和蛋白在3T3-L1细胞分化过程中的表达。在诱导分化的初期，Nur77在mRNA和蛋白质水平上都得到了快速、瞬时的诱导，并且几乎完全定位在细胞核中。异丁基甲基黄嘌呤对Nur77蛋白的诱导是必不可少的，它至少部分地通过保护蛋白质免受蛋白酶体的快速降解而起作用。Nur77siRNA导致3T3-L1细胞脂肪生成延迟，并伴随有丝分裂克隆扩张延迟。这些作用至少部分是通过下调细胞周期蛋白D和E的表达来实现的。Nur77的组成性表达抑制了3T3-L1细胞的脂肪生成，同时细胞周期蛋白DI的表达增强，并延长了有丝分裂的克隆扩张。此外，Nur77的结构性表达抑制了N1H-3T3细胞的成脂作用，但瞬时诱导促进了N1H-3T3细胞的成脂。这些结果表明，Nur77通过调节细胞周期进程来加速脂肪细胞的分化，而快速而短暂的诱导是其作用的关键。
Nur77 is an orphan member of the nuclear receptor superfamily that is expressed in various types of cells and mediates diverse biological processes. Although Nur77 mRNA is induced in the early stage of adipogenesis of 3T3-L1 cells, its roles are not known. To address this issue, we closely inspected the expression of Nur77 mRNA and protein during differentiation of 3T3-L1 cells. Nur77 was induced rapidly and transiently at both mRNA and protein levels only in the initial phase of differentiation induction, and localized almost exclusively in the nuclei. Isobutylmethylxanthine was essential for the induction of Nur77 protein, acting by at least in part protecting the protein from rapid degradation by proteasome. Nur77 siRNA resulted in delayed adipogenesis in 3T3-L1, accompanied by retarded mitotic clonal expansion. These effects were mediated at least partly by decreased expression of cyclins D and E. Constitutive expression of Nur77 inhibited adipogenesis of 3T3-L1, accompanied by enhanced expression of cyclin DI and prolonged mitotic clonal expansion. Moreover, constitutive expression of Nur77 inhibited, but transient induction of Nur77 promoted, adipogenesis in N1H-3T3 cells. These results suggest that Nur77 accelerates adipocyte differentiation by regulating cell cycle progression and the rapid and transient induction is crucial for its action.