Liippo J, Nera K P, Veistinen E, Lähdesmäki A, Postila V, Kimby E, Riikonen P, Hammarström L, Pelkonen J, Lassila O
Turku Graduate School of Biomedical Sciences and Department of Medical Microbiology, University of Turku, Turku, Finland.
Eur J Immunol. 2001 Dec;31(12):3469-74. doi: 10.1002/1521-4141(200112)31:12<3469::aid-immu3469>3.0.co;2-g.
Aiolos is a chromatin remodeling transcription regulator that plays an antiproliferative role in B lymphocyte function. In contrast to the related Ikaros factors, mammalian Aiolos has not been reported to generate splice variants. In addition, although human leukemic lymphoblasts express non-DNA-binding Ikaros isoforms with potential dominant negative effect on other interacting factors,the role of Aiolos in human lymphoid disorders has remained obscure. To address the question, why Aiolos should delineate from Ikaros in such a marked way, we have here analyzed whether also human Aiolos could generate alternate isoforms. According to the results obtained, both normal and neoplastic B lineage cells were found to express at least five novel Aiolos variants. Also structurally dominant negative variants with less than three DNA-binding domains were identified. In conclusion, given the multiplicity of also human Aiolos isoforms and thereby the evidently more intricate contribution of Aiolos to the chromatin remodeling machinery, it is suggested, that not only Ikaros, but also Aiolos could participate in a more versatile manner in the regulation of B lymphocyte function.
Aiolos是一种染色质重塑转录调节因子,在B淋巴细胞功能中发挥抗增殖作用。与相关的Ikaros因子不同,尚未有报道称哺乳动物的Aiolos会产生剪接变体。此外,尽管人类白血病淋巴母细胞表达对其他相互作用因子具有潜在显性负效应的非DNA结合Ikaros异构体,但Aiolos在人类淋巴系统疾病中的作用仍不清楚。为了解决为什么Aiolos会以如此显著的方式与Ikaros区分开来这个问题,我们在此分析了人类Aiolos是否也能产生可变异构体。根据所得结果,发现正常和肿瘤性B系细胞均表达至少五种新型Aiolos变体。还鉴定出了具有少于三个DNA结合结构域的结构上显性负变体。总之,鉴于人类Aiolos异构体的多样性以及由此Aiolos对染色质重塑机制的贡献显然更为复杂,建议不仅Ikaros,而且Aiolos也可能以更通用的方式参与B淋巴细胞功能的调节。