HTLV-I encoded Tax in association with NF-kappa B precursor p105 enhances nuclear localization of NF-kappa B p50 and p65 in transfected cells.
HTLV-I encoded Tax in association with NF-kappa B precursor p105 enhances nuclear localization of NF-kappa B p50 and p65 in transfected cells.
复制标题
HTLV-I编码的Tax与NF-κB前体p105结合增强了转染细胞中NF-κB p50和p65的核定位。
作者：
M. Watanabe;M. Muramatsu;H. Hirai;T. Suzuki;J. Fujisawa;M. Yoshida;K. Arai;N. Arai
NF-κ B是由两个亚基p50和p65组成的异源二聚体蛋白，并通过与抑制蛋白I κ B结合而作为无活性形式被隔离在细胞质中。在本研究中，使用COS-7表达系统研究HTLV-1编码的Tax对外源表达的NF-κ B B p105（编码p50的前体）的影响。当p105在COS-7细胞中表达时，前体p105和经加工的p50通过彼此缔合而保留在胞质组分中，并且在核组分中未检测到p50。在共表达p105和Tax的细胞中，胞质组分中的p50/p105比率随着核组分中p50的诱导而降低，这引起NF-κ B结合活性的显著增加。增强NF-κ B结合活性没有观察到腺病毒编码的E1 A和牛乳头状瘤病毒编码的E2，并与Tax与p105相关的能力。当缺乏锚蛋白基序重复序列的p105 delta X在该系统中表达时，在核部分中检测到p105 delta X和加工的p50，并且p50/p105 delta X比率不受与Tax共表达的影响。在相同的表达系统中，外源表达的NF-κ B p65被p105保留在细胞质中，Tax的进一步表达允许p65进入细胞核。这些结果表明，在该模型系统中，p105作为I κ B将p50和p65隔离在细胞质中，Tax通过抑制p105的I κ B活性，增强p50和p65的核定位。这些发现为Tax诱导核内NF-κ B的新机制提供了可能性。
NF-kappa B is a heterodimeric protein composed of two subunits, p50 and p65, and is sequestered in the cytoplasm as an inactive form through the association with an inhibitory protein, I kappa B. In the present study, the effect of HTLV-I encoded Tax on the exogenously expressed NF-kappa B p105, which encodes a precursor of p50, was investigated using a COS-7 expression system. When p105 was expressed in COS-7 cells, the precursor p105 and the processed p50 were retained in the cytosolic fraction by associating each other, and p50 was not detected in the nuclear fraction. In the cells co-expressing p105 and Tax, the p50/p105 ratio in the cytosolic fraction reduced with an induction of p50 in the nuclear fraction, which gave rise to a significant increase in NF-kappa B binding activity. Enhancement of NF-kappa B binding activity was not observed by adenovirus encoded E1A and bovine papilloma virus encoded E2, and correlated well with the ability of Tax to associate with p105. When p105 delta X which lacks the repeats of the ankyrin motif was expressed in this system, p105 delta X and processed p50 were detected in the nuclear fraction and p50/p105 delta X ratio was not affected by co-expression with Tax. In the same expression system, exogenously expressed NF-kappa B p65 was retained in the cytoplasm by p105 and further expression of Tax allowed entry of p65 in the nucleus. These results suggest that, in this model system, p105 acts as an I kappa B to sequester p50 and p65 in the cytoplasm and that Tax by inhibiting I kappa B activity of p105, enhances nuclear localization of p50 and p65. These findings raise a possibility for a novel mechanism for the induction of NF-kappa B in the nucleus by Tax.