Loss of CBP causes T cell lymphomagenesis in synergy with p27Kip1 insufficiency
Loss of CBP causes T cell lymphomagenesis in synergy with p27Kip1 insufficiency
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DOI：
10.1016/s1535-6108(04)00022-4
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发表时间：
2004-02-01
期刊：
影响因子：
50.3
通讯作者：
van Deursen, JMA
中科院分区：
文献类型：
--
作者：
Kang-Decker, N;Tong, CL;van Deursen, JMA
CBP可以作为肿瘤抑制因子发挥作用，但在其缺失的情况下控制肿瘤发生的机制尚不清楚。在这里，我们表明，CBP在小鼠胸腺细胞失活导致淋巴瘤。虽然CBP与p53的反式激活功能有关，但这些肿瘤的发展似乎并不涉及p53活性的丧失。CBP无效肿瘤显示P27（Kip 1）水平降低，细胞周期蛋白E和Skp 2水平升高，这两种癌蛋白可促进p27（Kip 1）蛋白水解。通过将p27（Kip 1）-null等位基因引入CBP敲除小鼠来减少p27（Kip 1），加速了淋巴瘤的发生，并且似乎减少了Skp 2和细胞周期蛋白E上调的需要。这些数据表明，CBP的损失介导淋巴瘤的合作机制，减少p27（Kip 1）丰度。
CBP can function as a tumor suppressor, but the mechanisms that govern oncogenesis in its absence are unknown. Here we show that CBP inactivation in mouse thymocytes leads to lymphoma. Although CBP has been implicated in the transactivation functions of p53, development of these tumors does not seem to involve loss of p53 activity. CBP-null tumors show reduced levels of P27(Kip1) and increased levels of cyclin E andSkp2, two oncoproteins that can promote p27(Kip1) proteolysis. Reduction of p27(Kip1) by introduction of a p27(Kip1)-null allele into CBP knockout mice accelerates lymphomagenesis and seems to obviate the requirement for Skp2 and cyclin E upregulation. These data suggest that CBP loss mediates lymphomagenesis in cooperation with a mechanism that reduces p27(Kip1) abundance.