Figure 3. Lack of Acetylation at Its DNA-Binding Domain and C Terminus Abolishes p53 Ability to Induce Cell Growth Arrest.
(A) Expression of the human p53 protein at physiological levels in Tet-off-p53 H1299 cells. The total cell extracts from Tet-off-p53 cells (before and after induction) and HCT116 cells (treated without and with etoposide) were assayed by western blot using the antibodies against p53 (DO-1) and actin.
(B) Acetylation of p53 in Tet-off-p53 cells. The Flag-p53 proteins enriched from Tet-off-p53 and Tet-off-p53-8KR cells by M2 immunoprecipitation were subjected to western blot analysis using acetylation- and phosphorylation-specific antibodies, as indicated, and anti-p53 (1801) to determine the levels of total p53.
(C) Tet-off-p53 and Tet-off-p53-8KR cells were induced for 0, 1, 2, 3, and 4 days. The total cell extracts were analyzed by western blot using antibodies against p53 (DO-1), Mdm2, Bax, Puma, Pig3, p21, and actin.
(D) Four days after induction, Tet-off-p53 and Tet-off-p53-8KR cells were treated with 10 μM Brdu for 1 hr and immunostained with the anti-BrdU antibody. The nuclei are in blue (DAPI), and Brdu-positive nuclei are shown in red.
(E) Tet-off-p53 and Tet-off-p53-8KR cells were induced as in (C), and incorporation of BrdU was assayed as in (D).