Yuen P H, Khang Y H, Matherne C
University of Texas System Cancer Center, Science Park-Research Division, Smithville 78957.
Leukemia. 1992;6 Suppl 3:76S-82S.
Changing nucleotide 3 of the CORE consensus from T to C has no effect on the binding of a 42 kDa protein, which has little affinity for the CCAAT binding site. Changing nucleotide 6 of the CORE consensus from T to C significantly reduces binding of the 42 kDa protein. Studies on the pathology induced by various MoMuLV mutants with CORE mutations showed that the CORE elements are important in modulating virulence in T-cell lymphomagenesis in BALB/c mice. However, disease specificity appears to be influenced as much by the host as it is by the virus. LVa is preferentially bound to the GRE-LVa sites. Deletion of nucleotide 9 and changing nucleotides 10 and 11 from GG to AA in the GRE-LVa element does not disrupt binding of LVa. Changing nucleotide 10 from G to A and nucleotide 13 from A to T in the GRE-LVa element does not disrupt binding of GR but allows binding of a novel protein which displaces or abolishes binding of LVa. These five nucleotide changes alone do not alter disease specificity and had a minimal effect on virulence in T-cell lymphomagenesis in BALB/c mice. Additionally, changing nucleotide 3 in CORE(a) and nucleotide 6 in CORE(b) does not alter disease specificity but has a small additional effect on virulence in T-cell lymphomagenesis.
将核心共有序列的第3位核苷酸由T变为C，对一种42 kDa蛋白的结合没有影响，该蛋白对CCAAT结合位点的亲和力很低。将核心共有序列的第6位核苷酸由T变为C，显著降低了42 kDa蛋白的结合。对具有核心突变的各种莫洛尼鼠白血病病毒（MoMuLV）突变体诱导的病理学研究表明，核心元件在调节BALB/c小鼠T细胞淋巴瘤发生中的毒力方面很重要。然而，疾病特异性似乎受到宿主的影响与受到病毒的影响一样大。LVa优先结合到GRE-LVa位点。在GRE-LVa元件中删除第9位核苷酸并将第10和11位核苷酸从GG变为AA，不会破坏LVa的结合。将GRE-LVa元件中的第10位核苷酸从G变为A以及第13位核苷酸从A变为T，不会破坏GR的结合，但允许一种新蛋白结合，该新蛋白取代或消除LVa的结合。仅这五个核苷酸变化不会改变疾病特异性，并且对BALB/c小鼠T细胞淋巴瘤发生中的毒力影响最小。此外，改变CORE(a)中的第3位核苷酸和CORE(b)中的第6位核苷酸不会改变疾病特异性，但对T细胞淋巴瘤发生中的毒力有微小的额外影响。
