Studies of the immortalizing activity of HTLV type 1 Tax, using an infectious molecular clone and transgenic mice.

Studies of the immortalizing activity of HTLV type 1 Tax, using an infectious molecular clone and transgenic mice.
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使用感染性分子克隆和转基因小鼠研究 HTLV 1 型 Tax 的永生活性。

DOI:
10.1089/08892220050193092
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发表时间:
2000
期刊:
AIDS research and human retroviruses.
影响因子:
--
通讯作者:
Grossman,W
Grossman,W
中科院分区:
--
文献类型:
--
作者:
Ratner,L;Portis,T;Robek,M;Harding,J;Grossman,W

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Tax在转基因小鼠的成熟淋巴区室中的表达导致自然杀伤细胞和细胞毒性T淋巴细胞的淋巴增殖性恶性肿瘤。转基因小鼠肿瘤表现出 p53肿瘤抑制基因的突变和野生型p53蛋白的功能失活。p53基因杂合的Tax转基因小鼠表现出更快的肿瘤扩散和加速的肿瘤转移。 mortality.在HTLV-1感染性克隆中Tax反式激活的研究证明了核因子B激活在淋巴细胞永生化中的关键作用。一个破坏税务激活的突变体 cAMP反应元件结合(CREB)蛋白的表达导致CD 8+淋巴细胞优先永生化,而不是CD 4+淋巴细胞优先永生化 野生型感染性克隆破坏Tax与CREB结合蛋白CBP相互作用的突变不影响感染性分子克隆的淋巴细胞永生化。这些模型提供 对HTLV-1白血病发生的分子细节的新见解。
Expression of Tax in the mature lymphoid compartment of transgenic mice resulted in a lymphoproliferative malignancy of natural killer cells and cytotoxic T lymphocytes. Transgenic mouse tumors exhibited mutations in the p53 tumor suppressor gene, and functional inactivation of wild-type p53 protein. Tax transgenic mice heterozygous for the p53 gene exhibited more rapid tumor dissemination and accelerated mortality. Studies of Taxtrans-activation in an infectious clone of HTLV-1 demonstrated a critical role for nuclear factor B activation in lymphocyte immortalization. A mutant disrupting Tax activation of the cAMP response element binding (CREB) protein resulted in preferential immortalization of CD8+lymphocytes, rather than preferential immortalization of CD4+lymphocytes seen with the wild-type infectious clone. A mutation disrupting Tax interaction with CREB-binding protein, CBP, did not affect lymphocyte immortalization by the infectious molecular clone. These models provide new insights into the molecular details of HTLV-1 leukemogenesis.
DOI: --
发表时间: 2008
期刊:
影响因子: --
作者:
1 Minagawa;J.
通讯作者: J.
DOI: 10.1083/jcb.106.1.29
发表时间: 1988-01
影响因子: 7.8
作者:
de Hostos, E L;Togasaki, R K;Grossman, A
通讯作者: Grossman, A