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BMC Cancer. 2017 Nov 28;17(1):795. doi: 10.1186/s12885-017-3787-2.

Sertad1 antagonizes iASPP function by hindering its entrance into nuclei to interact with P53 in leukemic cells.

Author information

1
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC), 288 Nanjing Road, Tianjin, 300020, People's Republic of China.
2
State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College (CAMS & PUMC), 288 Nanjing Road, Tianjin, 300020, People's Republic of China. wangjx@ihcams.ac.cn.

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.

KEYWORDS:

Apoptosis; Leukemic cell; P53; Sertad1; iASPP

PMID:
29179704
PMCID:
PMC5704379
DOI:
10.1186/s12885-017-3787-2
[Indexed for MEDLINE]
Free PMC Article

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