Barz Thomas, Ackermann Karin, Dubois Gaelle, Eils Roland, Pyerin Walter
Biochemische Zellphysiologie (B0200) and Intelligente Bioinformatiksysteme (H0900), Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
J Cell Sci. 2003 Apr 15;116(Pt 8):1563-77. doi: 10.1242/jcs.00352.
Protein kinase CK2, a vital, pleiotropic and highly conserved serine/threonine phosphotransferase is involved in transcription-directed signaling, gene control and cell cycle regulation and is suspected to play a role in global processes. Searching for these global roles, we analyzed the involvement of CK2 in gene expression at cell cycle entry by using genome-wide screens. Comparing expression profiles of Saccharomyces cerevisiae wild-type strains with strains with regulatory or catalytic subunits of CK2 deleted, we found significant alterations in the expression of genes at all cell cycle phases and often in a subunit- and isoform-specific manner. Roughly a quarter of the genes known to be regulated by the cell cycle are affected. Functionally, the genes are involved with cell cycle entry, progression and exit, including spindle pole body formation and dynamics. Strikingly, most CK2-affected genes exhibit no common transcriptional control features, and a considerable proportion of temporarily altered genes encodes proteins involved in chromatin remodeling and modification, including chromatin assembly, (anti-)silencing and histone (de-)acetylation. In addition, various metabolic pathway and nutritional supply genes are affected. Our data are compatible with the idea that CK2 acts at different levels of cellular organization and that CK2 has a global role in transcription-related chromatin remodeling.
蛋白激酶CK2是一种重要的、具有多效性且高度保守的丝氨酸/苏氨酸磷酸转移酶,参与转录导向信号传导、基因调控和细胞周期调节,并且被怀疑在整体过程中发挥作用。为了寻找这些整体作用,我们通过全基因组筛选分析了CK2在细胞周期进入时对基因表达的影响。比较酿酒酵母野生型菌株与缺失CK2调节亚基或催化亚基的菌株的表达谱,我们发现在所有细胞周期阶段基因表达都有显著变化,而且往往是以亚基和亚型特异性的方式。已知受细胞周期调控的基因中约有四分之一受到影响。从功能上讲,这些基因参与细胞周期的进入、进程和退出,包括纺锤极体的形成和动态变化。引人注目的是,大多数受CK2影响的基因没有共同的转录控制特征,并且相当一部分暂时改变的基因编码参与染色质重塑和修饰的蛋白质,包括染色质组装、(抗)沉默和组蛋白(去)乙酰化。此外,各种代谢途径和营养供应基因也受到影响。我们的数据与以下观点一致,即CK2在细胞组织的不同水平上发挥作用,并且CK2在与转录相关的染色质重塑中具有整体作用。