The Study On The Transcripition Activity Modulation Of C/EBPβ By C-Abl Non-Receptor Tyrosine Kinase

It was shown by the yeast two-hybrid experiment using kinase active full length c-Abl as bait protein that C/EBPβ may be one of the potential c-Abl interaction proteins. C/EBPβ, also known as nuclear factor for interleukin (IL)-6 expression (NF-IL6) in human, which was expressed in many tissues such as adipose tissue, hematopoietic tissue, liver, kidney and spleen, is involved in differentiation, acute phase reactions, adipogenesis, inflammation, and hematopoiesis. However, the mechanism responsible for the regulation of C/EBPP in cells is not well known.The c-Abl non-receptor tyrosine kinases and its transforming variants have been implicated in many important cellular processes, such as cell proliferation, survival, cell adhension and migration. The effects of c-Abl are mediated by multiple protein-protein or protein-DNA interactions. In this study, direct interaction between C/EBPβ and c-Abl or Arg was demonstrated by co-immunoprecipiation, in vitro binding and GST-pull down assay. It was also shown that SH2 and SH3 domain of c-Abl interact with C/EBPβ. C/EBPβ was phosphorylated by c-Abl or Arg at Y79 and thereby enhanced the transcription activity of C/EBPP's target gene, such as il-6 and hTOP1. The enhanced transcription activity of C/EBPp attributed to the tyrosine phosphorylation by c-Abl or Arg, which resulted in the increase of DNA-binding activity, higher stability of C/EBPβ and higher LAP/LIP ratio.It was well demonstrated that cyclin D1 play critical role in cell cycle regulation. During G2 phase, Ras induces expression of cyclin D₁, and the high cyclin D₁ level is maintained through G1 phase and are required for the initiation of S phase, and the level reduced at this stage, which is required for DNA...