CK2 phosphorylation of C/EBPδ regulates its transcription factor activity

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 8 (C/EBP delta) as a new substrate for CK2. Using point mutants of C/EBP delta the major phosphorylation site for CK2 was mapped to serine 57, which is located within the transactivation domain of C/EBP delta. For proper functioning as a transcription factor C/EBP delta has to be translocated into the nucleus where it forms heterodimers with other members of the C/EBP delta family of proteins and ATF4. Here, we found that CK2 phosphorylation does neither influence the subcellular localization of C/EBP delta nor its interaction with C/EBP delta, but rather does CK2 phosphorylation modulate the transcriptional activity of C/EBP delta. Moreover, we found that CK2 bound to C/EBP delta, which might help to target CK2 to the transcriptional machinery where it can phosphorylate other transcription factors or co-activators. (C) 2015 Elsevier Ltd. All rights reserved.