靶向多肽R8-HBAP抑制成人T细胞白血病细胞恶性增殖

R8-HBAP peptide suppresses ATL cell proliferation

成人T细胞白血病(Adult T-cell leukemia,ATL)是与人类T淋巴细胞白血病1型病毒(Human T-cell leukemia virus type 1,HTLV-1)感染密切相关的恶性淋巴细胞白血病.HTLV-1反义编码的HBZ(HTLV-1 b ZIP factor)蛋白在ATL发生过程中扮演极为重要的角色.为了寻找治疗成人T细胞白血病的方法,设计了能与HBZ蛋白形成二聚体,从而封闭HBZ蛋白功能的靶向多肽R8-HBAP.通过免疫共沉淀实验,发现R8-HBAP可以有效抑制HBZ蛋白与下游靶蛋白c-Jun的结合,报告基因实验显示,R8-HBAP能阻遏HBZ蛋白对AP-1信号通路的调控作用.MTT和流式细胞术实验发现,R8-HBAP能抑制ATL细胞的恶性增殖并促进细胞凋亡.因此,靶向多肽R8-HBAP通过阻遏HBZ蛋白的功能从而抑制白血病细胞的恶性增殖,为R8-HBAP的开发利用及成人T细胞白血病的治疗提供一定的实验依据.

Adult T-cell leukemia { ATL） was a peripheral T-cell neoplasm associated with irrfection by Human T-cell leukemia vfi＇us type 1 （ HTLV-1 ）. The HTLV-1 bZIP fzctor （ HBZ ）, which was encoded by minus strand of provirus, was thought to play a central role in the development of ATL. In order to find out the treat- ment of ATL, it was successfully designed and selected several HBZ specific inhibitory targeting peptides （R8-HBAP）. In immunoprecipitation assay, R8-HBAP could specifically associated with HBZ and therefore inhibited the interaction between HBZ and c-Jun. Reporter assay showed that R8-HBAP could overcome the repression of the AP-1 signaling by HBZ. MTT assay and flow cytometry revealed that R8-HBAP suppressed the proliferation of ATL cells and induced the apoptosis of ATL cells. In summary, R8-HBAP inhibited the proliferation of ATL cells by repressing the function of HBZ protein, and it would provide experimental basis for the further application of R8-HBAP and the treatment of adult T-cell leukemia.