Non-receptor tyrosine kinases c-Abl and Arg regulate the activity of C/EBPbeta.

Abstract

The CCAAT/enhancer-binding protein beta (C/EBPbeta) 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/EBPbeta 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/EBPbeta was phosphorylated by c-Abl or Arg. The phosphorylation of C/EBPbeta resulted in an increased C/EBPbeta stability and a potentiation of C/EBPbeta transcription activation activity in cells. Expression of the C/EBPbeta(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/EBPbeta; furthermore, the C/EBPbeta (Y79F) mutant induced an increased apoptosis compared to the wild type C/EBPbeta. These findings suggest that the c-Abl family non-receptor tyrosine kinases have a role in the regulation of the C/EBPbeta transcription factor.

• Authors: Xiaorong Li, Xuan Liu, Guangfei Wang, Xiaohui Zhu, Xiuhua Qu, Xiaoming Li, Yao Yang, Li Peng, Chufang Li, Ping Li, Wei Huang, Qingjun Ma, Cheng Cao
• Journal: Journal of molecular biology (J Mol Biol) Vol. 391 Issue 4 Pg. 729-43 (Aug 28 2009) ISSN: 1089-8638 [Electronic] Netherlands
• PMID: 19563810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCAAT-Enhancer-Binding Protein-beta
• Recombinant Fusion Proteins
• Tyrosine
• ARG tyrosine kinase
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-abl

Topics

• Animals
• Apoptosis (physiology)
• CCAAT-Enhancer-Binding Protein-beta (genetics, metabolism)
• Cell Cycle (physiology)
• Cell Line
• Fibroblasts (cytology, physiology)
• Humans
• Mice
• Mice, Knockout
• Phosphorylation
• Protein-Tyrosine Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-abl (genetics, metabolism)
• RNA Interference
• Recombinant Fusion Proteins (genetics, metabolism)
• Transcription, Genetic
• Tyrosine (metabolism)