Involvement of BH3-only proteins in hematologic malignancies

被引:34
作者
Kuroda, Junya [1 ]
Taniwaki, Masafumi [1 ]
机构
[1] Kyoto Prefectural Univ Med, Dept Med, Div Hematol & Oncol, Kamigyo Ku, Kyoto 6028566, Japan
关键词
Apoptosis; Bcl-2; family; BH3-only protein; BH3-mimetics; Bim; Chemotherapy; Hematologic malignancies; Therapeutic targeting; LYMPHOCYTIC-LEUKEMIA CELLS; SMALL-MOLECULE INHIBITOR; BCL-X-L; PATHWAY PROMOTES PHOSPHORYLATION; GLUCOCORTICOID-INDUCED APOPTOSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; SMALL INTERFERING RNA; BIM MESSENGER-RNA; FAMILY-MEMBER BIM;
D O I
10.1016/j.critrevonc.2008.10.004
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The interaction between anti-apoptotic and pro-apoptotic members of the Bcl-2 family proteins determines life or death for cancer cells. In this context, BH3-only proteins (such as Bim), members of the pro-apoptotic Bcl-2 family proteins, act as key initiators of apoptosis by activating Bax and Bak through liberating them from anti-apoptotic Bcl-2 members. This then leads to the disruption of mitochondrial outer membrane, and eventually promotes proteolytic cascades for cellular dismantling. We here review the growing evidence of how BH3-only proteins are involved in tumorigenesis and in apoptosis induced by anti-cancer agents in hematologic malignancies. A deeper understanding of the roles of BH3-only proteins in cell death regulation may yield crucial insights for the further development of more effective and rational cell killing strategies. Recent developments in the direct therapeutic manipulation of Bcl-2 proteins using BH3-mimicking agents, such as ABT-737 or GX15-070, for hematologic malignancies are also summarized. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:89 / 101
页数:13
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