在真核生物中，过氧化物酶体通过调控其生物发生，与内质网及线粒体等细胞器协作，完成脂肪酸代谢及自由基清除等重要的生理过程，但该调控过程的机制仍待深入研究。酿酒酵母的酪蛋白激酶CK2参与调控线粒体和内质网的蛋白转运系统，而我们的前期研究结果表明，CK2可以磷酸化修饰过氧化物酶体膜蛋白受体Pex19以及基质蛋白转运体中的关键蛋白Pex14，暗示CK2可能是调控多个细胞器发生的关键因子。本项目拟围绕CK2调控过氧化物酶体生物发生的分子机制开展系列工作，首先在参与过氧化物酶体发生的蛋白中全面筛选CK2的底物并鉴定其磷酸化位点；进而系统研究Pex14及Pex19等CK2底物的磷酸化对过氧化物酶体生物发生过程的调控，从而揭示CK2调控过氧化物酶体蛋白转运及从头合成等发生过程的信号通路。本课题对于理解过氧化物酶体与其它细胞器协作的调控方式有重要意义。

Peroxisomes participate in diverse biochemical reactions, such as lipid metabolism and scavenging reactive oxygen species, by regulating their biogenesis and coordinating with endoplasmic reticulum (ER) and mitochondria. However, the regulatory mechanisms underlying peroxisome biogenesis remain elusive. It is also not clear how peroxisomes coordinating with other organelles. It has been shown that Saccharomyces cerevisiae casein kinase 2 (CK2) regulates the protein import into mitochondria and ER. Our preliminary data indicates that CK2 directly phosphorylates peroxisomal membrane protein receptor Pex19 and one of the essential components of peroxisomal translocon, Pex14, in Saccharomyces cerevisiae. Furthermore, CK2 maintains the stability of Pex14 and Pex19. Based on these data, we propose to dissect the molecular mechanisms underlying how CK2 regulates the peroxisome biogenesis through phosphorylating the Pex14, Pex19 and etc. First, by in vitro kinase assay, we are going to screen all CK2 substrates involved in peroxisome biogenesis and indentify the critical CK2 phosphorylation sites on them. Second, we will investigate whether peroxisome biogenesis is affected by phosphorylation of these CK2 substrates. Finally, we will dissect the signal transduction pathway of how CK2 pariticipates in peroxisomal matrix and membrane protein import, and peroxisome de novo synthesis. This project will provide important information on how CK2 regulates peroxisome biogenesis and pave the road toward understanding how peroxisomes coordinating with ER and mitochondria.