Role of TAp73alpha in induction of apoptosis by transforming growth factor-beta in gastric cancer cells.
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.
Yamamura
Yasuko
Y
Oncology Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Lee
Wei Lin
WL
Goh
Mei Xian
MX
Ito
Yoshiaki
Y
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D050687:E2F1 Transcription Factor / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D013274:Stomach Neoplasms / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein