Graduate School of Life Science, Hokkaido University, Sapporo 060-8589, Japan.
Biochem Biophys Res Commun. 2013 Jun 28;436(2):289-94. doi: 10.1016/j.bbrc.2013.05.095. Epub 2013 Jun 4.
DJ-1, a product of the DJ-1/PARK7 gene, has been suggested to play various functions involved in transcriptional regulation, protease activity, anti-oxidative stress activity, and regulation of mitochondrial complex I. Such a variety of functions of DJ-1 are supposed to be realized through interactions with different partner proteins. Among the candidates for DJ-1-partner proteins detected in TOF-MAS analyses of the cellular proteins co-immunoprecipitated with DJ-1, we focused here pyrroline-5-carboxylate reductase 1, PYCR1, a final key enzyme for proline biosynthesis. DJ-1 directly bound to PYCR1 in vivo and in vitro. DJ-1 and PYCR1 colocalized in mitochondria, and both were suggested to be involved in regulation of mitochondrial membrane potential, but differently. DJ-1 enhanced the enzymatic activity of PYCR1 in vitro. The cells knocked down for DJ-1 and PYCR1 showed lower viability under oxidative stress conditions. No additive nor synergistic results were obtained for the cells that had been knocked down for both DJ-1 and PYCR1, suggesting that DJ-1 and PYCR1 are on the same pathway of anti-oxidative stress protection of the cells.
DJ-1 是 DJ-1/PARK7 基因的产物，被认为具有多种功能，包括参与转录调控、蛋白酶活性、抗氧化应激活性和调节线粒体复合物 I。DJ-1 的这些多种功能被认为是通过与不同的伴侣蛋白相互作用来实现的。在使用 DJ-1 与 DJ-1 共免疫沉淀的细胞蛋白的 TOF-MAS 分析中检测到的 DJ-1 伴侣蛋白候选物中，我们在此重点关注吡咯啉-5-羧酸还原酶 1（PYCR1），它是脯氨酸生物合成的最终关键酶。DJ-1 体内和体外均直接与 PYCR1 结合。DJ-1 和 PYCR1 在线粒体中共定位，并且都被认为参与调节线粒体膜电位，但方式不同。DJ-1 体外增强了 PYCR1 的酶活性。敲低 DJ-1 和 PYCR1 的细胞在氧化应激条件下的存活率较低。敲低 DJ-1 和 PYCR1 的细胞没有表现出相加或协同作用，这表明 DJ-1 和 PYCR1 处于细胞抗氧化应激保护的同一途径上。
