Presence of potent transcriptional activation domains in the predisposing tuberous sclerosis (Tsc2) gene product of the Eker rat model.
Presence of potent transcriptional activation domains in the predisposing tuberous sclerosis (Tsc2) gene product of the Eker rat model.
复制标题
Eker 大鼠模型的易感结节性硬化症 (Tsc2) 基因产物中存在有效的转录激活域。
作者：
H. Tsuchiya;K. Orimoto;K. Kobayashi;O. Hino
Eker 大鼠遗传性肾癌是实验动物中孟德尔显性易患特定癌症的一个很好的例子。我们最近报道，人类结节性硬化症基因 (TSC2) 的大鼠同源物中的种系插入在 Eker 大鼠模型中引起显性遗传性癌症，并且 Tsc2 基因功能具有肿瘤抑制性质。我们还展示了大鼠和人类基因产物之间的强烈保守性。 Tsc2 基因产物（在人类中称为“马铃薯蛋白”）的分子功能尚不清楚，尽管它含有与 ras 家族 GTP 酶激活蛋白 (Rap1GAP) 同源的短氨基酸序列。在这里，我们描述了 Tsc2 产物羧基末端的转录激活域（AD1 和 AD2）（分别位于外显子 30 和 32 以及外显子 41 中）。 Eker 插入突变（内含子 30）破坏了它们的转录活性。 COOH 末端截短的 Tsc2 蛋白位于细胞核中，而全长蛋白主要存在于细胞质的核周区域。目前 Tsc2 基因转录激活域的证明为研究其在肾癌发生中的作用提供了线索。
The Eker rat hereditary renal carcinoma is an excellent example of Mendelian dominant predisposition to a specific cancer in an experimental animal. We recently reported that a germline insertion in the rat homologue of the human tuberous sclerosis gene (TSC2) gives rise to dominantly inherited cancer in the Eker rat model, as well as a tumor suppressor nature for the Tsc2 gene function. We also showed a strong conservation between the rat and human gene products. The molecular function of the Tsc2 gene product (called "tuberin" in the human case) is not yet understood, although it contains a short amino acid sequence homologous to ras family GTPase-activating proteins (Rap1GAP). Here, we describe transcriptional activation domains (AD1 and AD2) in the carboxyl terminus of the Tsc2 product (in exons 30 and 32 and exon 41, respectively). The Eker insertional mutation (intron 30) disrupts their transcriptional activity. Whereas a COOH-terminal truncated Tsc2 protein was localized in the nucleus, the full-length protein is found predominantly in the perinuclear region of cytoplasm. The present demonstration of transcriptional activation domains in the Tsc2 gene provides clues for studying its role in renal carcinogenesis.
DOI：
10.1073/pnas.91.24.11413
发表时间：
1994-11-22
影响因子：
11.1
作者：
YEUNG, RS;XIAO, GH;KNUDSON, AG
通讯作者：
KNUDSON, AG
马铃薯蛋白基因的从头移码突变。
影响因子：
3.5
作者：
Kumar,A;Wolpert,C;Kandt,RS;Segal,J;Pufky,J;Roses,AD;Pericak-Vance,MA;Gilbert,JR
通讯作者：
Gilbert,JR