Identification of regions critical for the integrity of the TSC1-TSC2-TBC1D7 complex.
Identification of regions critical for the integrity of the TSC1-TSC2-TBC1D7 complex.
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DOI：
10.1371/journal.pone.0093940
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nellist M
中科院分区：
文献类型：
--
作者：
Santiago Lima AJ;Hoogeveen-Westerveld M;Nakashima A;Maat-Kievit A;van den Ouweland A;Halley D;Kikkawa U;Nellist M
TSC 1-TSC 2-TBC 1D 7复合物是雷帕霉素复合物1的机制靶标的重要负调节剂，其响应于环境线索控制细胞生长。失活TSC 1和TSC 2突变导致结节性硬化症（TSC），这是一种常染色体显性遗传疾病，其特征是在各种器官和组织中发生良性肿瘤，特别是大脑，皮肤和肾脏。在TSC患者中尚未报道TBC 1D 7突变，但TBC 1D 7的纯合失活可导致巨脑畸形和智力残疾。在这里，使用外显子特异性缺失策略，我们证明了TSC 1的某些区域对于TSC 1-TSC 2复合物的核心功能是不必要的。此外，我们发现TBC 1D 7结合位点是由TSC 1外显子22编码的，并确定了参与TSC 1-TBC 1D 7相互作用的氨基酸残基。
The TSC1-TSC2-TBC1D7 complex is an important negative regulator of the mechanistic target of rapamycin complex 1 that controls cell growth in response to environmental cues. Inactivating TSC1 and TSC2 mutations cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterised by the occurrence of benign tumours in various organs and tissues, notably the brain, skin and kidneys. TBC1D7 mutations have not been reported in TSC patients but homozygous inactivation of TBC1D7 causes megaencephaly and intellectual disability. Here, using an exon-specific deletion strategy, we demonstrate that some regions of TSC1 are not necessary for the core function of the TSC1-TSC2 complex. Furthermore, we show that the TBC1D7 binding site is encoded by TSC1 exon 22 and identify amino acid residues involved in the TSC1-TBC1D7 interaction.
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