Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells
Abstract Background As the important suppressor of P53, iASPP is found to be overexpressed in leukemia, and functions as oncogene that inhibited apoptosis of leukemia cells. Sertad1 is identified as one of the proteins that can bind with iASPP in our previous study by two-hybrid screen. Methods Co-i...
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| Format: | Article |
| Language: | English |
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BMC
2017-11-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3787-2 |
| _version_ | 1818533036109594624 |
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| author | Shaowei Qiu Shuang Liu Tengteng Yu Jing Yu Min Wang Qing Rao Haiyan Xing Kejing Tang Yinchang Mi Jianxiang Wang |
| author_facet | Shaowei Qiu Shuang Liu Tengteng Yu Jing Yu Min Wang Qing Rao Haiyan Xing Kejing Tang Yinchang Mi Jianxiang Wang |
| author_sort | Shaowei Qiu |
| collection | DOAJ |
| description | Abstract Background As the important suppressor of P53, iASPP is found to be overexpressed in leukemia, and functions as oncogene that inhibited apoptosis of leukemia cells. Sertad1 is identified as one of the proteins that can bind with iASPP in our previous study by two-hybrid screen. Methods Co-immunoprecipitation and immunofluorescence were perfomed to identified the interaction between iASPP and Sertad1 protein. Westernblot and Real-time quantitative PCR were used to determine the expression and activation of proteins. Cell proliferation assays, cell cycle and cell apoptosis were examined by flow cytometric analysis. Results iASPP combined with Sertad1 in leukemic cell lines and the interaction occurred in the cytoplasm near nuclear membrane. iASPP could interact with Sertad1 through its Cyclin-A, PHD-bromo, C terminal domain, except for S domain. Overexpression of iASPP in leukemic cells resulted in the increased cell proliferation and resistance to apoptosis induced by chemotherapy drugs. While overexpression of iASPP and Sertad1 at the same time could slow down the cell proliferation, lead the cells more vulnerable to the chemotherapy drugs, the resistance to chemotherapeutic drug in iASPPhi leukemic cells was accompanied by Puma protein expression. Excess Sertad1 protein could tether iASPP protein in the cytoplasm, further reduced the binding between iASPP and P53 in the nucleus. Conclusions Sertad1 could antagonize iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells when iASPP was in the stage of overproduction. |
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| language | English |
| last_indexed | 2024-12-11T17:53:22Z |
| publishDate | 2017-11-01 |
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| series | BMC Cancer |
| spelling | doaj.art-16f64e89a2b746eb90b37a97ca5d22212022-12-22T00:56:09ZengBMCBMC Cancer1471-24072017-11-0117111110.1186/s12885-017-3787-2Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cellsShaowei Qiu0Shuang Liu1Tengteng Yu2Jing Yu3Min Wang4Qing Rao5Haiyan Xing6Kejing Tang7Yinchang Mi8Jianxiang Wang9State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC)Abstract Background As the important suppressor of P53, iASPP is found to be overexpressed in leukemia, and functions as oncogene that inhibited apoptosis of leukemia cells. Sertad1 is identified as one of the proteins that can bind with iASPP in our previous study by two-hybrid screen. Methods Co-immunoprecipitation and immunofluorescence were perfomed to identified the interaction between iASPP and Sertad1 protein. Westernblot and Real-time quantitative PCR were used to determine the expression and activation of proteins. Cell proliferation assays, cell cycle and cell apoptosis were examined by flow cytometric analysis. Results iASPP combined with Sertad1 in leukemic cell lines and the interaction occurred in the cytoplasm near nuclear membrane. iASPP could interact with Sertad1 through its Cyclin-A, PHD-bromo, C terminal domain, except for S domain. Overexpression of iASPP in leukemic cells resulted in the increased cell proliferation and resistance to apoptosis induced by chemotherapy drugs. While overexpression of iASPP and Sertad1 at the same time could slow down the cell proliferation, lead the cells more vulnerable to the chemotherapy drugs, the resistance to chemotherapeutic drug in iASPPhi leukemic cells was accompanied by Puma protein expression. Excess Sertad1 protein could tether iASPP protein in the cytoplasm, further reduced the binding between iASPP and P53 in the nucleus. Conclusions Sertad1 could antagonize iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells when iASPP was in the stage of overproduction.http://link.springer.com/article/10.1186/s12885-017-3787-2iASPPSertad1P53ApoptosisLeukemic cell |
| spellingShingle | Shaowei Qiu Shuang Liu Tengteng Yu Jing Yu Min Wang Qing Rao Haiyan Xing Kejing Tang Yinchang Mi Jianxiang Wang Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells BMC Cancer iASPP Sertad1 P53 Apoptosis Leukemic cell |
| title | Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells |
| title_full | Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells |
| title_fullStr | Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells |
| title_full_unstemmed | Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells |
| title_short | Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells |
| title_sort | sertad1 antagonizes iaspp function by hindering its entrance into nuclei to interact with p53 in leukemic cells |
| topic | iASPP Sertad1 P53 Apoptosis Leukemic cell |
| url | http://link.springer.com/article/10.1186/s12885-017-3787-2 |
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