Selective killing of Burkitt's lymphoma cells by mBAFF-targeted delivery of PinX1.
Selective killing of Burkitt's lymphoma cells by mBAFF-targeted delivery of PinX1.
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通过 mBAFF 靶向递送 PinX1 选择性杀死伯基特淋巴瘤细胞
DOI：
10.1038/leu.2010.261
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发表时间：
2011-02
期刊：
影响因子：
11.4
通讯作者：
He, F.
中科院分区：
文献类型：
--
作者：
Zhang, L.;Jiang, Y.;Zheng, Y.;Zeng, Y.;Yang, Z.;Huang, G.;Liu, D.;Gao, M.;Shen, X.;Wu, G.;Yan, X.;He, F.
BAFF（属于TNF家族的B细胞活化因子）及其受体的表达增加已在许多B细胞恶性肿瘤中被鉴定。可溶性人BAFF突变体（mBAFF），结合BAFF受体，但不能激活B淋巴细胞增殖，可能作为一个竞争性抑制剂的BAFF，并可能作为一个新的配体的BAFF受体阳性的恶性肿瘤的靶向治疗。Pin 2/TRF 1相互作用蛋白X1（PinX 1）是一种核仁蛋白，可有效抑制端粒酶活性，影响肿瘤发生。在这项研究中，我们产生了新的重组蛋白含有mBAFF，聚精氨酸束9 R和PinX 1（或其C/N末端），以靶向淋巴瘤细胞。融合蛋白PinX 1/C-G4 S-9 R-G4 S-mBAFF和PinX 1/C-9 R-mBAFF特异性结合并内化到BAFF受体阳性细胞中，随后诱导生长抑制和凋亡。融合蛋白的选择性细胞毒性是BAFF受体介导的过程，并且依赖于mBAFF、PinX 1/C和9 R。此外，融合蛋白通过抑制端粒酶活性和随之而来的端粒缩短特异性地杀死表达BAFF受体的伯基特淋巴瘤（BL）细胞。在植入Raji细胞的严重联合免疫缺陷（SCID）小鼠中使用PinX 1C-G4 S-9 R-G4 S-mBAFF的治疗实验显示出显著延长的存活时间，表明融合蛋白的体内抗肿瘤活性。这些结果提示PinX 1/C-G4 S-9 R-G4 S-mBAFF在BL的靶向治疗中具有潜力。
Increased expression of BAFF (B cell-activating factor belonging to the TNF family) and its receptors has been identified in numerous B-cell malignancies. A soluble human BAFF mutant (mBAFF), binding to BAFF receptors but failing to activate B-lymphocyte proliferation, may function as a competitive inhibitor of BAFF and may serve as a novel ligand for targeted therapy of BAFF receptor-positive malignancies. Pin2/TRF1-interacting protein X1 (PinX1), a nucleolar protein, potently inhibits telomerase activity and affects tumorigenicity. In this study, we generated novel recombinant proteins containing mBAFF, a polyarginine tract 9R and PinX1 (or its C/N terminal), to target lymphoma cells. The fusion proteins PinX1/C–G4S–9R–G4S–mBAFF and PinX1/C–9R–mBAFF specifically bind and internalize into BAFF receptor-positive cells, and subsequently induce growth inhibition and apoptosis. The selective cytotoxicity of the fusion proteins is a BAFF receptor-mediated process and depends on mBAFF, PinX1/C and 9R. Moreover, the fusion proteins specifically kill BAFF receptor-expressing Burkitt's lymphoma (BL) cells by inhibiting telomerase activity and the consequent shortening of telomeres. Therapeutic experiments using PinX1C–G4S–9R–G4S–mBAFF in severe combined immunodeficient (SCID) mice implanted with Raji cells showed significantly prolonged survival times, indicating the in vivo antitumor activity of the fusion protein. These results suggest the potential of PinX1/C–G4S–9R–G4S–mBAFF in targeted therapy of BL.
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APRIL 在癌症中过度表达：与肿瘤进展有关。
影响因子：
3.8
作者：
Moreaux, Jerome;Veyrune, Jean-Luc;De Vos, John;Klein, Bernard
通讯作者：
Klein, Bernard
DOI：
10.1038/nsb941
发表时间：
2003-07-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
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作者：
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通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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作者：
Park, Yuk Pheel;Kim, Kwang Dong;Lee, Hee Gu
通讯作者：
Lee, Hee Gu
影响因子：
158.5
作者：
Dave, Sandeep S.;Fu, Kai;Staudt, Louis M.
通讯作者：
Staudt, Louis M.