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Science癌症发生的负反馈机制

2018-12-06 23:38:12

Science:癌症发生的负反馈机制

生物通报道,密歇根大学医学院病理学系,内科学系的研究者揭示了ARNT在CD30介导的负反馈机制,该成果公布在一期的Science杂志上。

CD30是一肿瘤坏死因子受体的家族成员之一,在大量的淋巴性瘤中,CD30的表达量和信号发送都增强,尤其在Anaplastic large-cell lymphoma(ALCL)和Hodgkin’s lymphoma中表现明显。为了了解CD30的信号通路,研究小组应用affinity purification Strategy技术发现CD30在调节核因子kB(nuclear factor kB,NF-kB)的转录因子RelB亚单位过程中,能与aryl hydrocarbon receptor nuclear translocation(ARNT)结合产生生理功能。

研究者发现ALCL细胞系表现出ARNT表达量低,表现出在RelB募集NF-kB效应启动子方面存在缺陷,但是RelA却能担负起相似的,具有代偿RelB的能力,可促进NF-kB基因表达。

研究者认为,ARNT的功能在CD30的RelB信号过程中具有一个负反馈的机制。

生物通 小鱼

原文检索:The Aryl Hydrocarbon Nuclear Translocator Alters CD30-Mediated NF-B–Dependent Transcription

【Abstract】

Expression and signaling of CD30, a tumor necrosis factor receptor family member, is up-regulated in numerous lymphoid-derived neoplasias, most notably anaplastic large-cell lymphoma (ALCL) and Hodgkin's lymphoma. To gain insight into the mechanism of CD30 signaling, we used an affinity purification strategy that led to the identification of the aryl hydrocarbon receptor nuclear translocator (ARNT) as a CD30-interacting protein that modulated the activity of the RelB subunit of the transcription factor nuclear factor B (NF-B). ALCL cells that were deficient in ARNT exhibited defects in RelB recruitment to NF-B–responsive promoters, whereas RelA recruitment to the same sites was potentiated, resulting in the augmented expression of these NF-B–responsive genes. These findings indicate that ARNT functions in concert with RelB in a CD30-induced negative feedback mechanism.

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