FHL2 interacts with iASPP and impacts the biological functions of leukemia cells

被引:8
作者
Lu, Wenting [1 ,2 ,3 ]
Yu, Tengteng [1 ,2 ,3 ]
Liu, Shuang [1 ,2 ,3 ]
Li, Saisai [1 ,2 ,3 ]
Li, Shouyun [1 ,2 ,3 ]
Liu, Jia [1 ,2 ,3 ]
Xu, Yingxi [1 ,2 ,3 ]
Xing, Haiyan [1 ,2 ,3 ]
Tian, Zheng [1 ,2 ,3 ]
Tang, Kejing [1 ,2 ,3 ]
Rao, Qing [1 ,2 ,3 ]
Wang, Jianxiang [1 ,2 ,3 ]
Wang, Min [1 ,2 ,3 ]
机构
[1] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China
[2] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin 300020, Peoples R China
[3] Peking Union Med Coll, Tianjin 300020, Peoples R China
基金
中国国家自然科学基金;
关键词
FHL2; iASPP; biological functions; leukemia; LIM DOMAIN PROTEIN-2; DOWN-REGULATION; PROMOTES APOPTOSIS; CANCER; EXPRESSION; PROLIFERATION; SURVIVAL; ACTIVATION; INHIBITOR; FAMILY;
D O I
10.18632/oncotarget.16617
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
iASPP is an inhibitory member of apoptosis-stimulating proteins of p53 (ASPP) family, which inhibits p53-dependent apoptosis. iASPP was highly expressed in acute leukemia, inhibited leukemia cells apoptosis and promoted leukemogenesis. In order to clarify its mechanism, a yeast two-hybrid screen was performed and FHL2 was identified for the first time as one of the binding proteins of iASPP. FHL2 was highly expressed in K562 and Kasumi-1 cells. FHL2 and iASPP interacted with each other and co-localized in both nucleus and cytoplasm. Either FHL2 or iASPP silenced could reduce cell proliferation, induce cell cycle arrest at G0/G1 phase, and increase cell apoptosis. Western blot analysis showed that the level of p21 and p27 increased, CDK4, E2F1, Cyclin E and anti-apoptotic proteins Bcl-2 and Bcl-xL reduced. Interestingly, when FHL2 was knocked down, the protein expression level of iASPP also decreased. Similarly, the expression of FHL2 would reduce when iASPP was silenced. These results indicated that FHL2 might be a novel potential target for acute myelocytic leukemia treatment.
引用
收藏
页码:40885 / 40895
页数:11
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