Biochemical Analyses of Csx/Nkx2.5 Mutants and Their Structure–Function Relationship

International Journal of Molecular Sciences

Yun-Zi Chen¹  Hua Ying¹  Jing Zhang²  Wei Cheng²  Yuan-Xi Kang² 

[1] The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, 210093, China; E-mail

关键词: Csx/Nkx2.5;    sporadic human congenital heart diseases (CHD);    regions out of homeodomain;    biochemical characteristics;   

DOI  :  10.3390/i8040284

来源: mdpi

【 摘 要 】

A homeodomain-containing transcription factor Csx/Nkx2.5 is an important regulator of cardiogensis in mammals. There has been considerable interest in understanding determinants of the diverse cardiac phenotypes associated with Csx/Nkx2.5 mutations situated within or around the homeodomain in patients. To make clear of the functional properties of the regions out of homeodomain, we found that mutants locate outside of the homeodomain retained intact nuclear localization and have nearly normal or increased transcriptional activity but impaired DNA binding capability, the C-terminus region exhibits an inhibitory function on transcriptional activity of wild type Csx/Nkx2.5, and the NK2-Specific Domain is likely to facilitate both DNA binding and protein-protein interaction. In the current study, deletion mutant in homeodomain displayed extremely different biological appearance from the mutants with deletion outside of the homeodomain, these may explain the clinical observation that patients with missense situated outside the homeodomain were not associated with atrioventricular conduction disturbance.

【 授权许可】

Unknown   
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