Non-receptor tyrosine kinases c-Abl and Arg regulate the activity of C/EBPbeta.
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.
Li
Xiaorong
X
Beijing Institute of Biotechnology, China.
Liu
Xuan
X
Wang
Guangfei
G
Zhu
Xiaohui
X
Qu
Xiuhua
X
Li
Xiaoming
X
Yang
Yao
Y
Peng
Li
L
Li
Chufang
C
Li
Ping
P
Huang
Wei
W
Ma
Qingjun
Q
Cao
Cheng
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl