c-Abl tyrosine kinase activates p21 transcription via interaction with p53.
c-Abl non-receptor tyrosine kinase has been implicated in many cellular processes including cell differentiation, stress response and regulating gene transcription. The mechanism by which c-Abl is involved in the regulation of gene transcription remains to be elucidated. In this study, we investigated the functions of c-Abl in the activation of p21 promoter. Our results showed that overexpression of c-Abl tyrosine kinase activated p21 promoter and endogenous p21 transcription in U2OS cells. We found that p53 is involved in the activation of p21 promoter by c-Abl, and integrative structure of p53 is required for regulating p21 transcription. In addition, the chromatin immunoprecipitation study demonstrated that c-Abl and p53 can be recruited to the region containing p53 binding site of p21 promoter, and c-Abl increases the DNA binding activity of p53 to the p21 promoter. Furthermore, not only the activation of p21 promoter but also the recruitment to p21 promoter by c-Abl is dependent on the interaction between c-Abl and p53 protein.
Jing
Yuqi
Y
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Wang
Min
M
Tang
Wen
W
Qi
Tianyang
T
Gu
Chunsheng
C
Hao
Shui
S
Zeng
Xianlu
X
D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D016315:Proto-Oncogene Proteins c-abl