Non-receptor Tyrosine Kinases c-Abl and Arg Regulate the Activity of C/EBPβ

Abstract: The CCAAT/enhancer-binding protein beta (C/EBPβ) is a critical transcription factor that regulates gene expression during numerous biological processes, including differentiation, metabolism, homeostasis, proliferation, tumorigenesis, inflammation, and apoptosis. In this study, interactions between C/EBPβ and either the Abelson murine leukemia viral oncogene homolog 1 (c-Abl) or the Abl-related gene (Arg) were demonstrated in vitro and in vivo with a direct binding assay and by co-immunoprecipitation, respectively. The Y79 amino acid residue of C/EBPβ was phosphorylated by c-Abl or Arg. The phosphorylation of C/EBPβ resulted in an increased C/EBPβ stability and a potentiation of C/EBPβ transcription activation activity in cells. Expression of the C/EBPβ(Y79F) mutant in HEK293, and K562, and in other cell lines, resulted in less of a delay in the cell cycle compared to the wild type C/EBPβ; furthermore, the C/EBPβ (Y79F) mutant induced an increased apoptosis compared to the wild type C/EBPβ. These findings suggest that the c-Abl family non-receptor tyrosine kinases have a role in the regulation of the C/EBPβ transcription factor. [Copyright &y& Elsevier]