来自美国芝加哥大学霍华德休斯医学研究所的科学家日前研究表明不同谱系特异性BTB-ZF转录因子可以招募CUL3以改变它们相关的染色质修饰复合物的泛素化模式。这些新的功能对于指导一些T细胞或B细胞效应程序的分化至关重要,并可能也与白血病和淋巴瘤中PLZF和BCL6的致癌作用相关。

-2012年11月22日《自然》

中文翻译


【题目】BTB-ZF因子招募E3连接酶cullin 3以调控淋巴效应程序

【译文】免疫系统中一些T细胞或B细胞效应因子程序的分化是由诱导快速表观遗传重塑的信号转录因子所指导的。本研究报道了早幼粒细胞白血病锌指蛋白(PLZF),指导自然杀伤细胞胸腺细胞类先天性效应因子程序的TBTB锌指(BTB-ZF)转录因子与cullin 3 (CUL3)显著相关,CUL3是一种先前研究表明利用含BTB结构域蛋白作为底物结合接头的E3泛素连接酶。PLZF转运CUL3至核内,在核内这两种蛋白在染色质修饰复合物中发生互作。而且,PLZF表达会引起该复合物一些组分的选择性泛素化改变。CUL3还被发现与BTB-ZF转录因子BCL6相关,BCL6可以指导生发中心B细胞和滤泡辅助性T细胞程序。小鼠中CUL3条件性缺失证实了CUL3在PLZF和BCL6依赖的谱系发育中的必要作用。我们得到如下结论,即不同谱系特异性BTB-ZF转录因子可以招募CUL3以改变它们相关的染色质修饰复合物的泛素化模式。我们认为这种新的功能对于指导一些T细胞或B细胞效应程序的分化至关重要,并可能也与白血病和淋巴瘤中PLZF和BCL6的致癌作用相关。

英文原稿


[Title]: BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs

[Authors]:Rebecca Mathew,1 Michael P. Seiler,1 Seth T. Scanlon,1 Ai-ping Mao,1 Michael G. Constantinides,1 Clara Bertozzi-Villa,1 Jeffrey D. Singer2 & Albert Bendelac1

[Abstract]The differentiation of several T- and B-cell effector programs in the immune system is directed by signature transcription factors that induce rapid epigenetic remodelling. Here we report that promyelocytic leukaemia zinc finger (PLZF), the BTB-zinc finger (BTB-ZF) transcription factor directing the innate-like effector program of natural killer T-cell thymocytes, is prominently associated with cullin 3 (CUL3), an E3 ubiquitin ligase previously shown to use BTB domain-containing proteins as adaptors for substrate binding. PLZF transports CUL3 to the nucleus, where the two proteins are associated within a chromatin-modifying complex. Furthermore, PLZF expression results in selective ubiquitination changes of several components of this complex. CUL3 was also found associated with the BTB-ZF transcription factor BCL6, which directs the germinal-centre B cell and follicular T-helper cell programs. Conditional CUL3 deletion in mice demonstrated an essential role for CUL3 in the development of PLZF- and BCL6-dependent lineages. We conclude that distinct lineage-specific BTB-ZF transcription factors recruit CUL3 to alter the ubiquitination pattern of their associated chromatin-modifying complex. We propose that this new function is essential to direct the differentiation of several T- and B-cell effector programs, and may also be involved in the oncogenic role of PLZF and BCL6 in leukaemias and lymphomas.

原文地址

http://www.nature.com/nature/journal/v491/n7425/full/nature11548.html

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