Interaction of TAp73 and breast cancer-associated gene 3 enhances the sensitivity of cervical cancer cells in response to irradiation-induced apoptosis.
Identification of proteins that are involved in the sensitivity of radiotherapy of cancers is important to enhance the response to cancer treatment. Expression of TAp73 is associated with the sensitivity of radiotherapy in cervical cancer patients, suggesting it plays an important role in controlling radiosensitivity. Here, by using yeast two-hybrid system, we identify breast cancer-associated gene 3 (BCA3) as the first and novel protein interacting partner of TAp73. By coimmunoprecipitation and Western blot analysis, we confirm that TAp73 binds with and stabilizes BCA3 in cervical cancer cell line HeLa. Immunofluorescence staining indicates that BCA3 is localized in the cytoplasm and nucleus. Interestingly, when coexpressed with TAp73, BCA3 interacts and colocalizes with TAp73 at the mitochondria. Mutagenesis reveals that the oligomerization domain of TAp73 is responsible for the interaction with BCA3. Furthermore, BCA3 augments the transactivation activity of TAp73 on bax promoter and protein expression. In addition, the expression of BCA3 also increases the sensitivity of TAp73-transfected cells in response to gamma-irradiation-induced apoptosis. Western blot analysis also shows that TAp73 and BCA3 induce activation of caspase-7 and caspase-9. In summary, these findings suggested that BCA3 is a novel protein partner of TAp73, and they cooperate with each other to exert tumor-suppressive functions and sensitize the response of cervical cancer cells to radiotherapy.
Leung
Thomas Ho-Yin
TH
Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, HKSAR.
Ngan
Hextan Yuen-Sheung
HY
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000528:radiation effects*; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D005720:Gamma Rays; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011836:Radiation Tolerance; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
C471621:AKIP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C494826:BAX protein, human; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D053179:Caspase 7; D053453:Caspase 9