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Transforming growth factor-beta (TGF-beta) is implicated as a tumor suppressor because it eliminates cancer cells from normal tissues by inhibiting cell growth and inducing apoptosis. Although p53 tumor suppressor is required for TGF-beta-induced p21 WAF1 expression and cell growth inhibition, its role in TGF-beta-induced apoptosis remains unclear. Here, we report that TAp73alpha, which is a member of the p53 family, binds to p53-binding sites in the promoters of proapoptotic Bax and Puma to activate their transcription, and mediates TGF-beta-induced apoptosis in gastric cancer cells. Our findings reveal a novel role of TAp73alpha in the induction of apoptosis by TGF-beta in cancer cells.
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Yamamura et al. (2008) studied this question.
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