N-terminal hamartin-binding and C-terminal GAP domain of tuberin can separate in vivo
N-terminal hamartin-binding and C-terminal GAP domain of tuberin can separate in vivo
复制标题
DOI：
10.1016/j.bbrc.2007.03.036
复制
发表时间：
2007-05-11
影响因子：
3.1
通讯作者：
Hino, Okio
中科院分区：
文献类型：
--
作者：
Momose, Shuji;Kobayashi, Toshiyuki;Hino, Okio
Eker大鼠是肾癌发生的动物模型，并在Tsc 2（结节性硬化症-2）基因中携带转座子插入。我们以前产生的转基因Eker大鼠和确定的Tsc 2基因的编码序列，负责抑制肾癌的Eker大鼠。Tsc 2-RGH是一种表达Tsc 2产物（tuberin）羧基末端区域（氨基酸1425-1755）的转基因，可部分抑制肾癌发生。然而，Tsc 2-DRG，它表达的突变体缺乏羧基末端区域（Δ aa 1425-1755），没有抑制肾癌的发生。在这里，我们发现在Eker大鼠中引入Tsc 2-RGH和Tsc 2-DRG完全抑制了肾癌发生，并以互补的方式从胚胎致死性中拯救了纯合子（Tsc 2（Ek/Ek））突变体。Tsc 2-RGH和Tsc 2-DRG的共同引入，而不是单独引入，有效地抑制了p70 S6 K的磷酸化。因此，N-末端错构蛋白结合和C-末端肿瘤抑制的功能结构域可以在体内分离。(c)2007年爱思唯尔公司All rights reserved.
The Eker rat is an animal model of renal carcinogenesis and carries a transposon insertion in the Tsc2 (tuberous sclerosis-2) gene. We previously generated transgenic Eker rats and identified coding sequences in the Tsc2 gene that are responsible for suppression of renal carcinogenesis in Eker rats. Tsc2-RGH, a transgene that expresses the carboxy terminal region (amino acids 1425-1755) of the Tsc2 product (tuberin), partially suppressed renal carcinogenesis. However, Tsc2-DRG, which expresses a mutant tuberin lacking the carboxyterminal region (Delta aa 1425-1755), did not suppress renal carcinogenesis. Here, we found that introduction of both Tsc2-RGH and Tsc2-DRG in Eker rats completely suppressed renal carcinogenesis and rescued homozygous (Tsc2(Ek/Ek)) mutants from embryonic lethality in a complementary manner. Co-introduction of Tsc2-RGH and Tsc2-DRG, but not introduction of either alone, efficiently suppressed phosphorylation of p70 S6K. Thus, the functional domains of N-terminal hamartin binding and C-terminal tumor suppression in tuberin can separate in vivo. (c) 2007 Elsevier Inc. All rights reserved.