FIGURE 7.

Cooperative induction of apoptosis through p73 and PTEN. A, H1299 and cell line derivatives overexpressing p73, PTEN, or both were lysed, and whole cell extracts were probed with p73, PTEN, and GAPDH antibodies. B, H1299, H1299 (p73α), H1299 (PTEN), and H1299 (p73α/PTEN) cell lines were treated with 0–10 μm doxorubicin (dox) as indicated for 20 h. Cells were harvested, and whole cell lysates were probed for cleaved PARP and GAPDH. C, H1299, H1299 (p73α), H1299 (PTEN), and H1299 (p73α/PTEN) cell lines were treated with 10 μm doxorubicin for 8 and 16 h, and Western blots were probed as in B. Lane C, control. D, H1299 cell line derivatives (described in C) were treated with 10 μm cisplatin for 16 h, and lysates were probed with the indicated antibodies. E, H1299 stable cell lines for ShGFP or ShPTEN were treated with 10 μm cisplatin for 16 h, and lysates were probed with the indicated antibodies. F, model for p73-PTEN interactions stimulating p53-independent apoptosis. PTEN and p73 are present in the cytoplasmic fraction and have limited binding with each other. DNA damage signals nuclear p73/PTEN levels, which lead to an enhancement in p73-PTEN complex formation. The end result is recruitment of PTEN binding to the PUMA promoter by transcriptional activity of p73, which in turn enhances BAX activity.