文章基本信息

标题：A 3 base pair deletion in TBX1 leads to reduced protein expression and transcriptional activity
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作者：Yuejuan Xu ; Shaohai Fang ; Erge Zhang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/srep44165
语种：English
出版社：Springer Nature
摘要：Transcription factor TBX1 plays a pivotal role in heart development and has been implicated in 22q11.2 deletion syndrome. The structure of this protein has been elucidated, and several mutations have been identified that disrupt TBX1 localization, DNA/protein-binding, or mRNA expression. This study reports a mutation in the TBX1 gene that leads to significantly reduced expression of the mutant protein. A total of 773 conotruncal heart defect patients and 516 unrelated healthy control individuals were enrolled, none of which harbored a 22q11.2 deletion or duplication. We identified a mutation, c.303-305delGAA, located in the third exon of TBX1 that does not disrupt TBX1 mRNA expression or DNA binding activity, but results in decreased TBX1 protein levels and transcriptional activity. Through protein degradation studies we demonstrated that TBX1 is degraded primarily in proteasomes. Although the c.303-305delGAA mutation leads to low levels of the mutant protein, we found that increased protein degradation was not the cause, and we hypothesize that an alternate mechanism, such as translational inhibition, may be the cause.