Institute of Genetics, Johannes Gutenberg-Universität, Becherweg 32, 55128, Mainz, Germany.
Mol Genet Genomics. 2010 Feb;283(2):147-56. doi: 10.1007/s00438-009-0505-z. Epub 2009 Dec 24.
The T-box transcription factors TBX2 and TBX3 are overexpressed in many human cancers raising the need for a thorough understanding of the cellular function of these proteins. In Drosophila, there is one corresponding ortholog, Optomotor-blind (Omb). Currently, only two missense mutations are known for the two human proteins. Making use of the developmental defects caused by inactivation of omb, we have isolated and molecularly characterized four new omb mutations, three of them are missense mutations of amino acids fully conserved in all Tbx proteins. We interpret the functional defects in the framework of the known structure of the human TBX3 protein and provide evidence for loss of Omb DNA-binding activity in all three newly identified missense mutations.
T 盒转录因子 TBX2 和 TBX3 在许多人类癌症中过表达，这就需要深入了解这些蛋白质的细胞功能。在果蝇中，有一个对应的直系同源物，Optomotor-blind (Omb)。目前，仅知道这两种人类蛋白质有两个错义突变。利用 omb 失活引起的发育缺陷，我们分离并分子特征鉴定了四个新的 omb 突变，其中三个是所有 Tbx 蛋白中完全保守的氨基酸的错义突变。我们根据已知的人类 TBX3 蛋白结构解释了功能缺陷，并提供了所有三个新鉴定的错义突变中 Omb DNA 结合活性丧失的证据。
