Lipert Barbara, Wegrzyn Paulina, Sell Henrike, Eckel Juergen, Winiarski Marek, Budzynski Andrzej, Matlok Maciej, Kotlinowski Jerzy, Ramage Lindsay, Malecki Maciej, Wilk Waclaw, Mitus Jerzy, Jura Jolanta
Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.
Biochim Biophys Acta. 2014 Apr;1843(4):780-8. doi: 10.1016/j.bbamcr.2014.01.001. Epub 2014 Jan 10.
Monocyte chemoattractant protein-induced protein 1 (MCPIP1) encoded by the ZC3H12a gene (also known as Regnase-1) is involved in the regulation of degradation of mRNA of inflammatory modulators and for processing of pre-miRNA. These functions depend on the presence of the PIN domain. Moreover, MCPIP1 was described as a negative regulator of NF-κB and AP-1 signaling pathways although mechanisms underlying such activity remain unknown. We aimed at determining the role of MCPIP1 in adipogenesis. Here, we present evidence that Mcpip1 transcription is transiently activated during 3T3-L1 transition from pre- to adipocytes. However Mcpip1 protein expression is also strongly decreased at day one after induction of adipogenesis. Knockdown of Mcpip1 results in an upregulation of C/EBPβ and PPARγ mRNAs, whereas overexpression of MCPIP1 reduces the level of both transcription factors and impairs adipogenesis. MCPIP1-dependend modulation of C/EBPβ and PPARγ levels results in a modulation of the expression of downstream controlled genes. In addition, decreased C/EBPβ, but not PPARγ, depends on the activity of the MCPIP1 PIN domain, which is responsible for RNase properties of this protein. Together, these data confirm that MCPIP1 is a key regulator of adipogenesis.
由ZC3H12a基因（也称为Regnase-1）编码的单核细胞趋化蛋白诱导蛋白1（MCPIP1）参与炎症调节因子mRNA降解的调控以及前体微小RNA（pre-miRNA）的加工。这些功能依赖于PIN结构域的存在。此外，MCPIP1被描述为NF-κB和AP-1信号通路的负调节因子，尽管这种活性背后的机制尚不清楚。我们旨在确定MCPIP1在脂肪生成中的作用。在此，我们提供证据表明，在3T3-L1细胞从前脂肪细胞向脂肪细胞转变过程中，Mcpip1转录被短暂激活。然而，在脂肪生成诱导后的第1天，Mcpip1蛋白表达也显著降低。敲低Mcpip1会导致C/EBPβ和PPARγ mRNA上调，而MCPIP1的过表达会降低这两种转录因子的水平并损害脂肪生成。MCPIP1对C/EBPβ和PPARγ水平的依赖性调节导致下游受控基因表达的调节。此外，C/EBPβ水平的降低而非PPARγ水平的降低依赖于MCPIP1 PIN结构域的活性，该结构域负责该蛋白的核糖核酸酶特性。总之，这些数据证实MCPIP1是脂肪生成的关键调节因子。
