Schwind Lisa, Zimmer Andreas D, Götz Claudia, Montenarh Mathias
Medical Biochemistry and Molecular Biology, Saarland University, Building 44, D-66424 Homburg, Germany.
Medical Biochemistry and Molecular Biology, Saarland University, Building 44, D-66424 Homburg, Germany.
Int J Biochem Cell Biol. 2015 Apr;61:81-9. doi: 10.1016/j.biocel.2015.02.004. Epub 2015 Feb 11.
Protein kinase CK2 plays an essential role in cell viability in lower and higher eukaryotes. As a global regulator it phosphorylates and thereby regulates a broad array of cellular targets including a large number of transcription factors. Here, we have identified the CCAAT/enhancer binding protein δ (C/EBPδ) as a new substrate for CK2. Using point mutants of C/EBPδ the major phosphorylation site for CK2 was mapped to serine 57, which is located within the transactivation domain of C/EBPδ. For proper functioning as a transcription factor C/EBPδ has to be translocated into the nucleus where it forms heterodimers with other members of the C/EBP family of proteins and ATF4. Here, we found that CK2 phosphorylation does neither influence the subcellular localization of C/EBPδ nor its interaction with C/EBPβ, but rather does CK2 phosphorylation modulate the transcriptional activity of C/EBPδ. Moreover, we found that CK2 bound to C/EBPδ, which might help to target CK2 to the transcriptional machinery where it can phosphorylate other transcription factors or co-activators.
蛋白激酶CK2在低等和高等真核生物的细胞活力中起着至关重要的作用。作为一种全局调节因子，它通过磷酸化作用来调节众多细胞靶点，包括大量转录因子。在此，我们已确定CCAAT/增强子结合蛋白δ（C/EBPδ）是CK2的一种新底物。利用C/EBPδ的点突变体，CK2的主要磷酸化位点被定位到丝氨酸57，该位点位于C/EBPδ的反式激活结构域内。为了作为转录因子正常发挥功能，C/EBPδ必须转运至细胞核，在那里它与C/EBP蛋白家族的其他成员以及ATF4形成异源二聚体。在此，我们发现CK2磷酸化既不影响C/EBPδ的亚细胞定位，也不影响其与C/EBPβ的相互作用，而是CK2磷酸化调节了C/EBPδ的转录活性。此外，我们发现CK2与C/EBPδ结合，这可能有助于将CK2靶向转录机制，使其能够磷酸化其他转录因子或共激活因子。
