c-Fos activates and physically interacts with specific enzymes of the pathway of synthesis of polyphosphoinositides.
c-Fos activates and physically interacts with specific enzymes of the pathway of synthesis of polyphosphoinositides.
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DOI：
10.1091/mbc.e11-03-0259
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发表时间：
2011-12
影响因子：
3.3
通讯作者：
Caputto BL
中科院分区：
文献类型：
--
作者：
Alfonso Pecchio AR;Cardozo Gizzi AM;Renner ML;Molina-Calavita M;Caputto BL
c - Fos通过一种不依赖AP - 1的机制增加多磷酸肌醇的总体合成，该机制涉及激活CDP - 二酰甘油合酶和磷脂酰肌醇（PtdIns）4 - 激酶IIα，但不涉及PtdIns合酶或PtdIns 4 - 激酶IIβ。免疫共沉淀和荧光共振能量转移（FRET）实验表明，c - Fos仅与它所激活的酶发生物理结合。
癌蛋白c - Fos是一种广为人知的AP - 1转录因子。此外，这种蛋白与内质网结合并激活磷脂的合成。然而，c - Fos刺激磷脂合成的总体机制以及被激活的特定脂质途径尚不清楚。在此我们表明，诱导静止细胞重新进入生长会促进多磷酸肌醇标记的增加，这依赖于c - Fos的表达。我们还研究了c - Fos对磷脂酰肌醇及其磷酸化衍生物合成的刺激是否依赖于磷脂酰肌醇磷酸生物合成途径中酶的激活。我们发现c - Fos在体外激活CDP - 二酰甘油合酶和磷脂酰肌醇（PtdIns）4 - 激酶IIα，而未观察到磷脂酰肌醇合酶或PtdIns 4 - 激酶IIβ被激活。免疫共沉淀和荧光共振能量转移实验都一致表明c - Fos的N末端结构域与它所激活的酶之间存在物理相互作用。
c-Fos increases the overall synthesis of polyphosphoinositides by an AP-1–independent mechanism involving activation of CDP-diacylglycerol synthase and phosphatidylinositol (PtdIns) 4-kinase II α but not of PtdIns synthase or PtdIns 4-kinase II β. Coimmunoprecipitation and FRET experiments show that c-Fos physically associates only with the enzymes it activates. The oncoprotein c-Fos is a well-recognized AP-1 transcription factor. In addition, this protein associates with the endoplasmic reticulum and activates the synthesis of phospholipids. However, the mechanism by which c-Fos stimulates the synthesis of phospholipids in general and the specific lipid pathways activated are unknown. Here we show that induction of quiescent cells to reenter growth promotes an increase in the labeling of polyphosphoinositides that depends on the expression of c-Fos. We also investigated whether stimulation by c-Fos of the synthesis of phosphatidylinositol and its phosphorylated derivatives depends on the activation of enzymes of the phosphatidylinositolphosphate biosynthetic pathway. We found that c-Fos activates CDP-diacylglycerol synthase and phosphatidylinositol (PtdIns) 4-kinase II α in vitro, whereas no activation of phosphatidylinositol synthase or of PtdIns 4-kinase II β was observed. Both coimmunoprecipitation and fluorescence resonance energy transfer experiments consistently showed a physical interaction between the N-terminal domain of c-Fos and the enzymes it activates.