Zaiman A L, Lewis A F, Crute B E, Speck N A, Lenz J
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Virol. 1995 May;69(5):2898-906. doi: 10.1128/JVI.69.5.2898-2906.1995.
Core binding factor (CBF), also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1, is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses. The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes. CBF consists of two subunits, a DNA binding subunit, CBF alpha, and a second subunit, CBF beta, that stimulates the DNA binding activity of CBF alpha. One of the genes that encodes a CBF alpha subunit is AML1, also called Cbf alpha 2. This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias. An exogenously expressed Cbf alpha 2-encoded subunit (CBF alpha 2-451) stimulated transcription from the SL3 enhancer in P19 and HeLa cells. Activity was mediated through the core elements. Three different isoforms of CBF beta were also tested for transcriptional activity on the SL3 enhancer. The longest form, CBF beta-187, increased the transcriptional stimulation by CBF alpha 2-451 twofold in HeLa cells, although it had no effect in P19 cells. Transcriptional activation by CBF beta required binding to the CBF alpha subunit, as a form of CBF beta that lacked binding ability, CBF beta-148, failed to increase activity. These results indicated that at least in certain cell types, the maximum activity of CBF required both subunits. They also provided support for the hypothesis that CBF is a factor in T lymphocytes that is responsible for recognition of the SL3 cores. We also examined whether CBF could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus, Akv. This difference strongly affects transcription in T cells and leukemogenicity of SL3. However, no combination of CBF alpha and CBF beta subunits that we tested was able to distinguish the 1-bp difference in transcription assays. Thus, a complete understanding of how T cells recognize the SL3 core remains to be elucidated.
核心结合因子（CBF），也被称为多瘤病毒增强子结合蛋白2和SL3增强子因子1，是一种哺乳动物转录因子，它能与逆转录病毒鼠白血病病毒家族增强子内一个被称为核心的元件结合。SL3病毒的核心元件是该病毒诱导T细胞淋巴瘤能力以及病毒长末端重复序列在T淋巴细胞中转录活性的重要遗传决定因素。CBF由两个亚基组成，一个是DNA结合亚基CBFα，另一个是刺激CBFα DNA结合活性的亚基CBFβ。编码CBFα亚基的基因之一是AML1，也称为Cbfα2。该基因座在人类骨髓增殖性疾病和白血病中会因染色体易位而重排。外源性表达的Cbfα2编码亚基（CBFα2 - 451）可刺激P19和HeLa细胞中SL3增强子的转录。活性是通过核心元件介导的。还测试了三种不同的CBFβ同工型对SL3增强子的转录活性。最长的形式CBFβ - 187在HeLa细胞中使CBFα2 - 451的转录刺激增加了两倍，尽管在P19细胞中没有作用。CBFβ的转录激活需要与CBFα亚基结合，因为缺乏结合能力的CBFβ形式CBFβ - 148无法增加活性。这些结果表明，至少在某些细胞类型中，CBF的最大活性需要两个亚基。它们还为CBF是T淋巴细胞中负责识别SL3核心的因子这一假说提供了支持。我们还研究了CBF是否能够区分SL3增强子核心与非致白血病病毒Akv核心之间1个碱基对的差异。这种差异强烈影响T细胞中的转录和SL3的致白血病性。然而，我们测试的CBFα和CBFβ亚基的任何组合在转录测定中都无法区分这1个碱基对的差异。因此，对T细胞如何识别SL3核心的完整理解仍有待阐明。
