Protein kinase 2 (casein kinase 2 [CK2]) is a protein serine/threonine kinase involved in cell proliferation with an expression that is dysregulated in tumors. ICBP90, a transcription factor exhibiting antiapoptotic properties, has several putative CK2 phosphorylation sites. The aim of the present study was to investigate whether ICBP90 could behave as a CK2 substrate. We observed that ICBP90 was more efficiently phosphorylated by the free CK2a subunit than by the heterotetrameric CK2 (alpha(2), beta(2)). Our results suggest that CK2 is an important regulator of the transcriptional activity of ICBP90 and therefore of the antiapoptotic properties of ICBP90. We propose that the "ICBP90 family" members may be substrates for CK2.