Title:The p53-Bak Apoptotic Signaling Axis Plays an Essential Role in Regulating Differentiation of the Ocular Lens
Volume: 12
Issue: 8
Author(s): L. Gong, D. W.-C. Li, Y. Liu, S. -J. Liu, Y. -M. Xiao, W. -B. Liu, L. Xiao, J. Liu, S. Sun, W. Hu, X. Hu, M. Deng, L. Zhang, X. Zhang, W. Ji, S. Hui, Z. Xiong, Y. Fu, H. Tang, S. Fu, F. Liu and P. Chen
Affiliation:
Keywords:
Apoptosis, Bak, cataract, cell differentiation, lens, p53, signaling pathway, tumor suppressor, gene
expression, transcription regulation, apoptotic machinery, tumor, transcriptional factor, chromosome, ocular lens, cataractogenesis, antibodies, immunohistochemistry.
Abstract: The tumor suppressor p53 is a master regulator of apoptosis and also plays a key role in cell cycle
checking. In our previous studies, we demonstrated that p53 directly regulates Bak in mouse JB6 cells (Qin et
al. 2008. Cancer Research. 68(11):4150) and that p53-Bak signaling axis plays an important role in mediating
EGCG-induced apoptosis. Here, we demonstrate that the same p53-Bak apoptotic signaling axis executes an
essential role in regulating lens cell differentiation. First, during mouse lens development, p53 is expressed and
differentially phosphorylated at different residues. Associated with p53 expression, Bak is also significantly
expressed during mouse lens development. Second, human p53 directly regulates Bak promoter and Bak
expression in p53 knockout mice (p53-/-) was significantly downregulated. Third, during in vitro bFGF-induced
lens cell differentiation, knockdown of p53 or Bak leads to significant inhibition of lens cell differentiation.
Fourth, besides the major distribution of Bak in cytoplasm, it is also localized in the nucleus in normal lens or
bFGF-induced differentiating lens cells. Finally, p53 and Bak are co-localized in both cytoplasm and nucleus,
and their interaction regulates the stability of p53. Together, these results demonstrate for the first time that the
p53-Bak apoptotic signaling axis plays an essential role in regulating lens differentiation.
