Nellist Mark, Sancak Ozgur, Goedbloed Miriam A, Rohe Christan, van Netten Diana, Mayer Karin, Tucker-Williams Aimee, van den Ouweland Ans M W, Halley Dicky J J
Department of Clinical Genetics, Erasmus MC, 3015 GE Rotterdam, The Netherlands.
Eur J Hum Genet. 2005 Jan;13(1):59-68. doi: 10.1038/sj.ejhg.5201276.
Tuberous sclerosis is an autosomal dominant human disorder caused by inactivating mutations to either the TSC1 or TSC2 tumour suppressor gene. Hamartin and tuberin, the TSC1 and TSC2 gene products, interact and the tuberin-hamartin complex inhibits cell growth by antagonising signal transduction to downstream effectors of the mammalian target of rapamycin (mTOR) through the small GTPase rheb. Previously, we showed that pathogenic tuberin amino-acid substitutions disrupt the tuberin-hamartin complex. Here, we investigate how these mutations affect the role of tuberin in the control of signal transduction through mTOR. Our data indicate that specific amino-acid substitutions have distinct effects on tuberin function.
结节性硬化症是一种常染色体显性遗传病，由肿瘤抑制基因TSC1或TSC2的失活突变引起。TSC1和TSC2基因产物错构瘤蛋白和结节蛋白相互作用，结节蛋白 - 错构瘤蛋白复合物通过小GTP酶Rheb拮抗哺乳动物雷帕霉素靶蛋白（mTOR）下游效应器的信号转导，从而抑制细胞生长。此前，我们发现致病性结节蛋白氨基酸取代会破坏结节蛋白 - 错构瘤蛋白复合物。在此，我们研究这些突变如何影响结节蛋白在通过mTOR控制信号转导中的作用。我们的数据表明，特定的氨基酸取代对结节蛋白功能有不同影响。
